Dr. Delitto is a board certified complex general surgical oncologist with a focus on conditions of the liver, pancreas, and stomach. He is an assistant professor in Stanford Medicine’s Department of Surgery.

His education includes a decade of postgraduate training in complex general surgical oncology, as well as a PhD in immunology with an emphasis on cancer biology. He completed a clinical fellowship at Johns Hopkins University and continued his research at the postdoctoral level in the laboratory of Dr. Elizabeth Jaffee. His research focus is on advancing the field of cancer immunology and harnessing his findings to improve immunotherapies.

He was the principal investigator of two studies examining the immune response to pancreatic cancer, including one funded by the National Cancer Institute.

Dr. Delitto has presented the findings of his research at conferences such as the American Association for Cancer Research, Society for the Immunotherapy of Cancer, American Association of Immunologists, American College of Surgeons, Academic Surgical Congress and Pancreas Club. In addition to cancer immunology, he has also presented work focused on cancer cachexia, surgical outcomes, translational experimental models and a variety of other oncologic topics.

He has published original work in Nature Communications, the Journal of the National Cancer Institute, Cancer Research, Clinical Cancer Research, and other high impact journals. He is also a reviewer for Annals of Surgery, Scientific Reports, Surgery, Tumor Biology, Journal of Surgical Research, PLOS ONE, and the Journal of Translational Medicine.

Dr. Delitto has earned numerous honors related to clinical excellence, teaching and research. He is board certified by the American Board of Surgery and a member of the Society of Surgical Oncology, American Association for Cancer Research and American Association of Immunologists.

Clinical Focus

  • General Surgery
  • Pancreatic Cancer
  • Gastric Cancer
  • Bile Duct Cancers
  • Gallbladder Cancer
  • Sarcoma
  • Cancer Immunology

Academic Appointments

Administrative Appointments

  • John and Marva Warnock Faculty Scholar, Stanford University School of Medicine (2023 - Present)

Professional Education

  • Board Certification: American Board of Surgery, Complex General Surgical Oncology (2022)
  • Fellowship: Johns Hopkins University Surgery Program (2021) MD
  • Residency: University of Florida Dept of General Surgery (2019) FL
  • Board Certification: American Board of Surgery, General Surgery (2019)
  • PhD Training: University of Florida Office of the Registrar (2016) FL
  • Medical Education: University of Pittsburgh School of Medicine Registrar (2011) PA

2023-24 Courses

Stanford Advisees

All Publications

  • Hematoxylin and Eosin Architecture Uncovers Clinically Divergent Niches in Pancreatic Cancer. Tissue engineering. Part A Guo, J. L., Lopez, D. M., Mascharak, S., Foster, D. S., Khan, A., Davitt, M. F., Nguyen, A. T., Burcham, A. R., Chinta, M. S., Guardino, N. J., Griffin, M., Miller, E., Januszyk, M., Raghavan, S. S., Longacre, T. A., Delitto, D. J., Norton, J. A., Longaker, M. T. 2024


    Pancreatic ductal adenocarcinoma (PDAC) represents one of the only cancers with an increasing incidence rate and is often associated with intra- and peri-tumoral scarring, referred to as desmoplasia. This scarring is highly heterogeneous in extracellular matrix (ECM) architecture and plays complex roles in both tumor biology and clinical outcomes that are not yet fully understood. Using hematoxylin and eosin (H&E), a routine histological stain utilized in existing clinical workflows, we quantified ECM architecture in 85 patient samples to assess relationships between desmoplastic architecture and clinical outcomes such as survival time and disease recurrence. By utilizing unsupervised machine learning (ML) to summarize a latent space across 147 local (e.g. fiber length, solidity) and global (e.g. fiber branching, porosity) H&E-based features, we identified a continuum of histological architectures that were associated with differences in both survival and recurrence. Further, we mapped H&E architectures to a CO-Detection by indEXing (CODEX) reference atlas, revealing localized cell- and protein-based niches associated with outcome-positive vs. outcome-negative scarring in the tumor microenvironment. Overall, our study utilizes standard H&E staining to uncover clinically relevant associations between desmoplastic organization and PDAC outcomes, offering a translatable pipeline to support prognostic decision-making and a blueprint of spatial-biological factors for modeling by tissue engineering methods.

    View details for DOI 10.1089/ten.TEA.2024.0039

    View details for PubMedID 38874979

  • Natural history of undifferentiated pleomorphic sarcoma: Experience from the US Sarcoma Collaborative JOURNAL OF SURGICAL ONCOLOGY Makris, E. A., Tran, T. B., Delitto, D. J., Lee, B., Ethun, C. G., Grignol, V., Howard, J., Bedi, M., Gamblin, T., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Cullinan, D., Fields, R. C., Cardona, K., Poultsides, G., Kirane, A. 2024


    Undifferentiated pleomorphic sarcoma (UPS) is a relatively rare but aggressive neoplasm. We sought to utilize a multi-institutional US cohort of sarcoma patients to examine predictors of survival and recurrence patterns after resection of UPS.From 2000 to 2016, patients with primary UPS undergoing curative-intent surgical resection at seven academic institutions were retrospectively reviewed. Epidemiologic and clinicopathologic factors were reviewed by site of origin. Overall survival (OS), recurrence-free survival (RFS), time-to-locoregional (TTLR), time-to-distant recurrence (TTDR), and patterns of recurrence were analyzed.Of the 534 UPS patients identified, 53% were female, with a median age of 60 and median tumor size of 8.5 cm. The median OS, RFS, TTLR, and TTDR for the entire cohort were 109, 49, 86, and 46 months, respectively. There were no differences in these survival outcomes between extremity and truncal UPS. Compared with truncal, extremity UPS were more commonly amenable to R0 resection (87% vs. 75%, p = 0.017) and less commonly associated with lymph node metastasis (1% vs. 6%, p = 0.031). R0 resection and radiation treatment, but not site of origin (extremity vs. trunk) were independent predictors of OS and RFS. TTLR recurrence was shorter for UPS resected with a positive margin and for tumors not treated with radiation.For patients with resected extremity and truncal UPS, tumor size >5 cm and positive resection margin are associated with worse survival OS and RFS, irrespectively the site of origin. R0 surgical resection and radiation treatment may help improve these survival outcomes.

    View details for DOI 10.1002/jso.27620

    View details for Web of Science ID 001194891800001

    View details for PubMedID 38562002

  • Distal Pancreatectomy With and Without Celiac Axis Resection for Adenocarcinoma: A Comparison in the Era of Neoadjuvant Therapy Daniel, S. K., Hironaka, C., Ahmad, M., Delitto, D., Dua, M., Lee, B., Norton, J., Visser, B., Poultsides, G. SPRINGER. 2024: S202-S203
  • Single cell pharmacogenic pipeline identifies novel opportunities in uterine leiomyosarcoma Daniel, S. K., Foster, D., Nosrati, F., Korah, M., Fallah, M., Sun, B. J., Loftus, T., Hu, D., Dua, M., Visser, B., Poultsides, G., Kirane, A., Longaker, M., Ganjoo, K., Lee, B., Delitto, D. SPRINGER. 2024: S42
  • Fibroblasts in the aged pancreas drive pancreatic cancer progression. Cancer research Zabransky, D. J., Chhabra, Y., Fane, M. E., Kartalia, E., Leatherman, J. M., Hüser, L., Zimmerman, J. W., Delitto, D., Han, S., Armstrong, T. D., Guinn, S., Pramod, S., Thompson, E. D., Hughes, S. J., O'Connell, J., Egan, J. M., Jaffee, E. M., Weeraratna, A. T. 2024


    Pancreatic cancer is more prevalent in older individuals and often carries a poorer prognosis for them. The relationship between the microenvironment and pancreatic cancer is multifactorial, and age-related changes in non-malignant cells in the tumor microenvironment may play a key role in promoting cancer aggressiveness. Since fibroblasts have profound impacts on pancreatic cancer progression, we investigated whether age-related changes in pancreatic fibroblasts influence cancer growth and metastasis. Proteomics analysis revealed that aged fibroblasts secrete different factors than young fibroblasts, including increased growth/differentiation factor 15 (GDF-15). Treating young mice with GDF-15 enhanced tumor growth, while aged GDF-15 knockout mice showed reduced tumor growth. GDF-15 activated AKT, rendering tumors sensitive to AKT inhibition in an aged but not young microenvironment. These data provide evidence for how aging alters pancreatic fibroblasts and promotes tumor progression, providing potential therapeutic targets and avenues for studying pancreatic cancer while accounting for the effects of aging.

    View details for DOI 10.1158/0008-5472.CAN-24-0086

    View details for PubMedID 38330147

  • Overexpression of Senescence-Associated Genes, SFN and CDC6, Correlates with Poor Survival in Patients with Stage II Hepatocellular Carcinoma (HCC) Badshah, J., Subramanian, S., Melcher, M., Sasaki, K., Visser, B., Delitto, D., Pruett, T., Niedernhofer, L., Kirchner, V. ELSEVIER SCIENCE INC. 2024: S64
  • ASO Visual Abstract: Patterns of Recurrence after Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer and the Role for Adjuvant Radiation. Annals of surgical oncology Hui, C., Ewongwo, A., Lau, B., Fisher, G., Delitto, D., Poultsides, G., Ho, Q. A., Rahimy, E., Pollom, E., Chang, D. T., Vitzthum, L. K. 2023

    View details for DOI 10.1245/s10434-023-14475-3

    View details for PubMedID 37875741

  • Optimized Nuclei Isolation from Fresh and Frozen Solid Tumor Specimens for Multiome Sequencing. Journal of visualized experiments : JoVE Foster, D. S., Griffin, M., Januszyk, M., Delitto, D., Norton, J. A., Longaker, M. T. 2023


    Multiome sequencing, which provides same-cell/paired single-cell RNA- and the assay for transposase-accessible chromatin with sequencing (ATAC-sequencing) data, represents a breakthrough in our ability to discern tumor cell heterogeneity-a primary focus of translational cancer research at this time. However, the quality of sequencing data acquired using this advanced modality is highly dependent on the quality of the input material. Digestion conditions need to be optimized to maximize cell yield without sacrificing quality. This is particularly challenging in the context of solid tumors with dense desmoplastic matrices that must be gently broken down for cell release. Freshly isolated cells from solid tumor tissue are more fragile than those isolated from cell lines. Additionally, as the cell types isolated are heterogeneous, conditions should be selected to support the total cell population. Finally, nuclear isolation conditions must be optimized based on these qualities in terms of lysis times and reagent types/ratios. In this article, we describe our experience with nuclear isolation for the 10x Genomics multiome sequencing platform from solid tumor specimens. We provide recommendations for tissue digestion, storage of single-cell suspensions (if desired), and nuclear isolation and assessment.

    View details for DOI 10.3791/65831

    View details for PubMedID 37902368

  • Desmoplastic stromal signatures predict patient outcomes in pancreatic ductal adenocarcinoma. Cell reports. Medicine Mascharak, S., Guo, J. L., Foster, D. S., Khan, A., Davitt, M. F., Nguyen, A. T., Burcham, A. R., Chinta, M. S., Guardino, N. J., Griffin, M., Lopez, D. M., Miller, E., Januszyk, M., Raghavan, S. S., Longacre, T. A., Delitto, D. J., Norton, J. A., Longaker, M. T. 2023: 101248


    Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death. Hallmarks include desmoplasia with variable extracellular matrix (ECM) architecture and a complex microenvironment with spatially defined tumor, stromal, and immune populations. Nevertheless, the role of desmoplastic spatial organization in patient/tumor variability remains underexplored, which we elucidate using two technologies. First, we quantify ECM patterning in 437 patients, revealing architectures associated with disease-free and overall survival. Second, we spatially profile the cellular milieu of 78 specimens using codetection by indexing, identifying an axis of pro-inflammatory cell interactions predictive of poorer outcomes. We discover that clinical characteristics, including neoadjuvant chemotherapy status, tumor stage, and ECM architecture, correlate with differential stromal-immune organization, including fibroblast subtypes with distinct niches. Lastly, we define unified signatures that predict survival with areas under the receiver operating characteristic curve (AUCs) of 0.872-0.903, differentiating survivorship by 655 days. Overall, our findings establish matrix ultrastructural and cellular organizations of fibrosis linked to poorer outcomes.

    View details for DOI 10.1016/j.xcrm.2023.101248

    View details for PubMedID 37865092

  • Patterns of Recurrence After Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer and the Role for Adjuvant Radiation. Annals of surgical oncology Hui, C., Ewongwo, A., Lau, B., Fisher, G., Delitto, D., Poultsides, G., Ho, Q., Rahimy, E., Pollom, E., Chang, D. T., Vitzthum, L. K. 2023


    BACKGROUND: Improved treatment strategies are needed for patients with locally advanced gastric cancer with poor response to neoadjuvant chemotherapy. We aimed to describe patterns of failure for patients with no or partial response (NR, PR) to preoperative chemotherapy.PATIENTS AND METHODS: We analyzed patients with locally advanced gastric cancer treated from 2008 to 2022 with preoperative chemotherapy followed by surgery with D2 resection. We excluded patients who received radiation. Cumulative incidence of locoregional failure (LRF) and distant metastases (DM) were calculated. For patients with recurrent abdominal disease, hypothetical radiation clinical treatment volumes (CTV) were contoured on postoperative scans and compared with patterns of recurrence.RESULTS: A total of 60 patients were identified. The most used preoperative chemotherapy was FLOT (38.6%), followed by FOLFOX (30%) and ECF/ECX/EOX (23.3%). Four (6.7%), 40 (66.7%), and 9 patients (15%) had a complete pathologic response (CR), PR, and NR to neoadjuvant therapy, respectively. Among patients without a CR, 3-year overall and progression-free survival rates were 62.3% (95% CI 48-76.6%) and 51.3% (95% CI 36.9-65.7%), respectively. Three-year cumulative incidence of LRF and DM were 8.4% (95% CI 0.4-16.4%) and 41.0% (95% CI 26.3-55.4%), respectively. Absolute rates of patients having the first site of recurrence encompassed by a postoperative radiation CTV was 2.0% for patients without a CR and 0% for patients with NR.CONCLUSIONS: Patients with locally advanced gastric cancer with less than a CR to chemotherapy have poor outcomes due to high rates of DM. Adjuvant locoregional therapy such as radiation is unlikely to affect survival.

    View details for DOI 10.1245/s10434-023-14350-1

    View details for PubMedID 37755563

  • Mechanoresponsive Pancreatic Ductal Adenocarcinoma Cancer Associated Fibroblasts Shows an FAK-Dependent Subtype Divergent from Canonical Fibrotic TGFB-Pathway Dependence Foster, D., Delitto, D., Januszyk, M., Yost, K., Griffin, M., Guo, J., Guardino, N., Delitto, A., Chinta, M., Burcham, A., Nguyen, A., Bauer-, K., Berry, C., Kim, A., Nosrati, F., Wapnir, I., Chang, H., Norton, J. A., Longaker, M. SPRINGER. 2023: S30-S31
  • Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin. Cancer cell Foster, D. S., Januszyk, M., Delitto, D., Yost, K. E., Griffin, M., Guo, J., Guardino, N., Delitto, A. E., Chinta, M., Burcham, A. R., Nguyen, A. T., Bauer-Rowe, K. E., Titan, A. L., Salhotra, A., Jones, R. E., da Silva, O., Lindsay, H. G., Berry, C. E., Chen, K., Henn, D., Mascharak, S., Talbott, H. E., Kim, A., Nosrati, F., Sivaraj, D., Ransom, R. C., Matthews, M., Khan, A., Wagh, D., Coller, J., Gurtner, G. C., Wan, D. C., Wapnir, I. L., Chang, H. Y., Norton, J. A., Longaker, M. T. 2022


    Cancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment. CAFs were once thought to be a relatively uniform population of matrix-producing cells, but single-cell RNA sequencing has revealed diverse CAF phenotypes. Here, we further probed CAF heterogeneity with a comprehensive multiomics approach. Using paired, same-cell chromatin accessibility and transcriptome analysis, we provided an integrated analysis of CAF subpopulations over a complex spatial transcriptomic and proteomic landscape to identify three superclusters: steady state-like (SSL), mechanoresponsive (MR), and immunomodulatory (IM) CAFs. These superclusters are recapitulated across multiple tissue types and species. Selective disruption of underlying mechanical force or immune checkpoint inhibition therapy results in shifts in CAF subpopulation distributions and affected tumor growth. As such, the balance among CAF superclusters may have considerable translational implications. Collectively, this research expands our understanding of CAF biology, identifying regulatory pathways in CAF differentiation and elucidating therapeutic targets in a species- and tumor-agnostic manner.

    View details for DOI 10.1016/j.ccell.2022.09.015

    View details for PubMedID 36270275

  • Postoperative Chemotherapy is Associated with Improved Survival in Patients with Node-Positive Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy. World journal of surgery Ivey, G. D., Shoucair, S., Delitto, D. J., Habib, J. R., Kinny-Koster, B., Shubert, C. R., Lafaro, K. J., Cameron, J. L., Burns, W. R., Burkhart, R. A., Thompson, E. L., Narang, A., Zheng, L., Wolfgang, C. L., He, J. 2022


    BACKGROUND: Postoperative chemotherapy following pancreatic cancer resection is the standard of care. The utility of postoperative chemotherapy for patients who receive neoadjuvant therapy (NAT) is unclear.METHODS: Patients who underwent pancreatectomy after NAT with FOLFIRINOX or gemcitabine-based chemotherapy for non-metastatic pancreatic adenocarcinoma (2015-2019) were identified. Patients who received less than 2months of neoadjuvant chemotherapy or died within 90days from surgery were excluded.RESULTS: A total of 427 patients (resectable, 22.2%; borderline resectable, 37.9%; locally advanced, 39.8%) were identified with the majority (69.3%) receiving neoadjuvant FOLFIRINOX. Median duration of NAT was 4.1months. Following resection, postoperative chemotherapy was associated with an improved median overall survival (OS) (28.7 vs. 20.4months, P=0.006). Risk-adjusted multivariable modeling showed negative nodal status (N0), favorable pathologic response (College of American Pathologists score 0 & 1), and receipt of postoperative chemotherapy to be independent predictors of improved OS. Regimen, duration, and number of cycles of NAT were not significant predictors. Thirty-four percent (60/176) of node-positive and 50.1% (126/251) of node-negative patients did not receive postoperative chemotherapy due to poor functional status, postoperative complications, and patient preference. Among patients with node-positive disease, postoperative chemotherapy was associated with improved median OS (27.2 vs. 10.5months, P<0.001). Among node-negative patients, postoperative chemotherapy was not associated with a survival benefit (median OS, 30.9 vs. 36.9months; P=0.406).CONCLUSION: Although there is no standard NAT regimen for patients with pancreatic cancer, postoperative chemotherapy following NAT and resection appears to be associated with improved OS for patients with node-positive disease.

    View details for DOI 10.1007/s00268-022-06667-x

    View details for PubMedID 35861852

  • First Recurrence of Synovial Sarcoma Presenting With Solitary Pancreatic Mass CUREUS JOURNAL OF MEDICAL SCIENCE Narayan, R. R., Charville, G. W., Delitto, D., Ganjoo, K. N. 2022; 14 (6)
  • Age-related changes in pancreatic fibroblasts promote growth and progression of pancreatic cancer Zabransky, D. J., Chhabra, Y., Fane, M. E., Delitto, D., Zimmermann, J. W., Jaffee, E. M., Weeraratna, A. T. AMER ASSOC CANCER RESEARCH. 2022
  • First Recurrence of Synovial Sarcoma Presenting With Solitary Pancreatic Mass. Cureus Narayan, R. R., Charville, G. W., Delitto, D., Ganjoo, K. N. 2022; 14 (6): e26356


    Synovial sarcoma usually presents in the lower extremities and metastasizes to the lungs; however, unusual patterns of recurrence can occur. For patients with recurrent synovial sarcoma to a proximal peripancreatic lymph node, a pancreaticoduodenectomy or Whipple procedure is the best option for a cure. Lymph node metastasis from synovial sarcoma is exceptionally rare, and data guiding the use of the Whipple procedure for curative resection of metastatic synovial sarcoma are even more sparse. In this report, we describe the management of a patient with metastatic synovial sarcoma to a proximal peripancreatic lymph node with a pancreaticoduodenectomy.

    View details for DOI 10.7759/cureus.26356

    View details for PubMedID 35903565

    View details for PubMedCentralID PMC9326242

  • Surgical solution for a paraneoplastic neurodegenerative disorder. Trauma surgery & acute care open Muhammad, H., Strayve, D. G., Narayan, R. R., Blayney, D. W., Delitto, D. 2022; 7 (1): e000928

    View details for DOI 10.1136/tsaco-2022-000928

    View details for PubMedID 35574257

    View details for PubMedCentralID PMC9062873

  • Radiographic, Biochemical, or Pathologic Response to Neoadjuvant Chemotherapy in Resected Pancreatic Cancer: Which Is Best? Javadi, C., Chang, J., Forgo, E., Ahmad, M., Fisher, G. A., Chang, D. T., Delitto, D. J., Dua, M. M., Lee, B., Visser, B. C., Norton, J. A., Poultsides, G. A. SPRINGER. 2022: 351
  • Surgical solution for a paraneoplastic neurodegenerative disorder TRAUMA SURGERY & ACUTE CARE OPEN Muhammad, H., Strayve, D. G., Narayan, R. R., Blayney, D. W., Delitto, D. 2022; 7 (1)
  • Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection. Oncoimmunology Delitto, D., Zabransky, D. J., Chen, F., Thompson, E. D., Zimmerman, J. W., Armstrong, T. D., Leatherman, J. M., Suri, R., Lopez-Vidal, T. Y., Huff, A. L., Lyman, M. R., Guinn, S. R., Baretti, M., Kagohara, L. T., Ho, W. J., Azad, N. S., Burns, W. R., He, J., Wolfgang, C. L., Burkhart, R. A., Zheng, L., Yarchoan, M., Zaidi, N., Jaffee, E. M. 2021; 10 (1): 2001159


    Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC.

    View details for DOI 10.1080/2162402X.2021.2001159

    View details for PubMedID 34777919

    View details for PubMedCentralID PMC8583296

  • GSK3 suppression upregulates β-catenin and c-Myc to abrogate KRas-dependent tumors. Nature communications Kazi, A., Xiang, S., Yang, H., Delitto, D., Trevino, J., Jiang, R. H., Ayaz, M., Lawrence, H. R., Kennedy, P., Sebti, S. M. 2018; 9 (1): 5154


    Mutant KRas is a significant driver of human oncogenesis and confers resistance to therapy, underscoring the need to develop approaches that disable mutant KRas-driven tumors. Because targeting KRas directly has proven difficult, identifying vulnerabilities specific for mutant KRas tumors is an important alternative approach. Here we show that glycogen synthase kinase 3 (GSK3) is required for the in vitro and in vivo growth and survival of human mutant KRas-dependent tumors but is dispensable for mutant KRas-independent tumors. Further, inhibiting phosphorylation of GSK3 substrates c-Myc on T58 and β-catenin on S33/S37/T41 and their subsequent upregulation contribute to the antitumor activity of GSK3 inhibition. Importantly, GSK3 blockade inhibits the in vivo growth of G12D, G12V, and G12C mutant KRas primary and metastatic patient-derived xenografts from pancreatic cancer patients who progressed on chemo- and radiation therapies. This discovery opens new avenues to target mutant KRas-dependent cancers.

    View details for DOI 10.1038/s41467-018-07644-6

    View details for PubMedID 30514931

    View details for PubMedCentralID PMC6279809

  • Prognostic Value of Clinical vs Pathologic Stage in Rectal Cancer Patients Receiving Neoadjuvant Therapy. Journal of the National Cancer Institute Delitto, D., George, T. J., Loftus, T. J., Qiu, P., Chang, G. J., Allegra, C. J., Hall, W. A., Hughes, S. J., Tan, S. A., Shaw, C. M., Iqbal, A. 2018; 110 (5): 460-466


    Neoadjuvant chemoradiation is currently standard of care in stage II-III rectal cancer, resulting in tumor downstaging for patients with treatment-responsive disease. However, the prognosis of the downstaged patient remains controversial. This work critically analyzes the relative contribution of pre- and post-therapy staging to the anticipated survival of downstaged patients.The National Cancer Database (NCDB) was queried for patients with rectal cancer treated with transabdominal resection between 2004 and 2014. Stage II-III patients downstaged with neoadjuvant radiation were compared with stage I patients treated with definitive resection alone. Patients with positive surgical margins were excluded. Overall survival was evaluated using both Kaplan-Meier analyses and Cox proportional hazards models. All statistical tests were two-sided.A total of 44 320 patients were eligible for analysis. Survival was equivalent for patients presenting with cT1N0 disease undergoing resection (mean survival = 113.0 months, 95% confidence interval [CI] = 110.8 to 115.3 months) compared with those downstaged to pT1N0 from both cT3N0 (mean survival = 114.9 months, 95% CI = 110.4 to 119.3 months, P = .12) and cT3N1 disease (mean survival = 115.4 months, 95% CI = 110.1 to 120.7 months, P = .22). Survival statistically significantly improved in patients downstaged to pT2N0 from cT3N0 disease (mean survival = 109.0 months, 95% CI = 106.7 to 111.2 months, P < .001) and cT3N1 (mean survival = 112.8 months, 95% CI = 110.0 to 115.7 months, P < .001), compared with cT2N0 patients undergoing resection alone (mean survival = 100.0 months, 95% CI = 97.5 to 102.5 months). Multiple survival analysis confirmed that final pathologic stage dictated long-term outcomes in patients undergoing neoadjuvant radiation (hazard ratio [HR] of pT2 = 1.24, 95% CI = 1.10 to 1.41; HR of pT3 = 1.81, 95% CI = 1.61 to 2.05; HR of pT4 = 2.72, 95% CI = 2.28 to 3.25, all P ≤ .001 vs pT1; HR of pN1 = 1.50, 95% CI = 1.41 to 1.59; HR of pN2 = 2.17, 95% CI = 2.00 to 2.35, both P < .001 vs pN0); while clinical stage at presentation had little to no predictive value (HR of cT2 = 0.81, 95% CI = 0.69 to 0.95, P = .008; HR of cT3 = 0.83, 95% CI = 0.72 to 0.96, P = .009; HR of cT4 = 1.02, 95% CI = 0.85 to 1.21, P = .87 vs cT1; HR of cN1 = 0.96, 95% CI = 0.91 to 1.02, P = .19; HR of cN2 = 0.96, 95% CI = 0.86 to 1.08, P = .48 vs cN0).Survival in patients with rectal cancer undergoing neoadjuvant radiation is driven by post-therapy pathologic stage, regardless of pretherapy clinical stage. These data will further inform prognostic discussions with patients.

    View details for DOI 10.1093/jnci/djx228

    View details for PubMedID 29165692

    View details for PubMedCentralID PMC6279292

  • Human Pancreatic Cancer Cells Induce a MyD88-Dependent Stromal Response to Promote a Tumor-Tolerant Immune Microenvironment. Cancer research Delitto, D., Delitto, A. E., DiVita, B. B., Pham, K., Han, S., Hartlage, E. R., Newby, B. N., Gerber, M. H., Behrns, K. E., Moldawer, L. L., Thomas, R. M., George, T. J., Brusko, T. M., Mathews, C. E., Liu, C., Trevino, J. G., Hughes, S. J., Wallet, S. M. 2017; 77 (3): 672-683


    Cancer cells exert mastery over the local tumor-associated stroma (TAS) to configure protective immunity within the tumor microenvironment. The immunomodulatory character of pancreatic lysates of patients with cancer differs from those with pancreatitis. In this study, we evaluated the cross-talk between pancreatic cancer and its TAS in primary human cell culture models. Upon exposure of TAS to pancreatic cancer cell-conditioned media, we documented robust secretion of IL6 and IL8. This TAS response was MyD88-dependent and sufficient to directly suppress both CD4+ and CD8+ T-cell proliferation, inducing Th17 polarization at the expense of Th1. We found that patients possessed a similar shift in circulating effector memory Th17:Th1 ratios compared with healthy controls. The TAS response also directly suppressed CD8+ T-cell-mediated cytotoxicity. Overall, our results demonstrate how TAS contributes to the production of an immunosuppressive tumor microenvironment in pancreatic cancer. Cancer Res; 77(3); 672-83. ©2016 AACR.

    View details for DOI 10.1158/0008-5472.CAN-16-1765

    View details for PubMedID 27864347

    View details for PubMedCentralID PMC5290036

  • Targeting tumor tolerance: A new hope for pancreatic cancer therapy? Pharmacology & therapeutics Delitto, D., Wallet, S. M., Hughes, S. J. 2016; 166: 9-29


    With a 5-year survival rate of just 8%, pancreatic cancer (PC) is projected to be the second leading cause of cancer deaths by 2030. Most PC patients are not eligible for surgery with curative intent upon diagnosis, emphasizing a need for more effective therapies. However, PC is notoriously resistant to chemoradiation regimens. As an alternative, immune modulating strategies have recently achieved success in melanoma, prompting their application to other solid tumors. For such therapeutic approaches to succeed, a state of immunologic tolerance must be reversed in the tumor microenvironment and that has been especially challenging in PC. Nonetheless, knowledge of the PC immune microenvironment has advanced considerably over the past decade, yielding new insights and perspectives to guide multimodal therapies. In this review, we catalog the historical groundwork and discuss the evolution of the cancer immunology field to its present state with a specific focus on PC. Strategies currently employing immune modulation in PC are reviewed, specifically highlighting 66 clinical trials across the United States and Europe.

    View details for DOI 10.1016/j.pharmthera.2016.06.008

    View details for PubMedID 27343757