Sanjeeth Rajaram

All Publications

• The spectrum of radiation therapy options for craniopharyngioma: a systematic review. Journal of neuro-oncology Harary, P. M., Rajaram, S., Hori, Y. S., Park, D. J., Chang, S. D. 2025

  Abstract

  Craniopharyngiomas (CPs) are rare, slow-growing brain tumors which originate in the sellar region. CPs may present with symptoms secondary to compression of surrounding structures, particularly the pituitary gland, and surgical removal has traditionally been the mainstay of treatment. However, due to high recurrence rates for CPs, especially when gross total resection is not feasible, radiotherapy has played an increasingly significant role in their management. Here, we review radiation modalities, treatment settings, and future directions in the management of CP. In addition, we outline emerging therapeutic combinations involving targeted therapies.A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search of the MEDLINE/PubMed, Embase, and Web of Science databases was used for initial identification of articles. Included studies were then grouped into the following treatment modalities: conventional radiotherapy (CRT), intensity-modulated radiotherapy (IMRT), proton therapy, fractionated stereotactic radiotherapy (FSRT) /stereotactic radiosurgery (SRS), and brachytherapy.A total of 60 studies met inclusion criteria, comprising 3041 patients, with a median sample size of 33 (range: 10-242) and age ranging from 6 to 55. This review included 8, 15, 3, 12, and 29 reports corresponding to brachytherapy, CRT, IMRT, proton therapy, and FSRT/SRS, respectively. Proton therapy and FSRT had the highest median 5-year progression-free survival (PFS), with rates of 92% and 89%, respectively. IMRT and proton therapy were primarily investigated in pediatric patients (median ages of 8.2 and 10.3 years, respectively). By comparison, FSRT and SRS research has mainly been in adult cohorts.Precision radiotherapy appears to be associated with high rates of tumor control in CP, suggesting these approaches bear further investigation. Selection of the appropriate radiation modality from those reviewed likely depends on several patient-specific factors. Important considerations include tumor location and volume, patient age, prior treatments for CP, and patient preference.

  View details for DOI 10.1007/s11060-025-05001-4

  View details for PubMedID 40063185

  View details for PubMedCentralID 9379650

• Genomic predictors of radiation response: recent progress towards personalized radiotherapy for brain metastases. Cell death discovery Harary, P. M., Rajaram, S., Chen, M. S., Hori, Y. S., Park, D. J., Chang, S. D. 2024; 10 (1): 501

  Abstract

  Radiotherapy remains a key treatment modality for both primary and metastatic brain tumors. Significant technological advances in precision radiotherapy, such as stereotactic radiosurgery and intensity-modulated radiotherapy, have contributed to improved clinical outcomes. Notably, however, molecular genetics is not yet widely used to inform brain radiotherapy treatment. By comparison, genetic testing now plays a significant role in guiding targeted therapies and immunotherapies, particularly for brain metastases (BM) of lung cancer, breast cancer, and melanoma. Given increasing evidence of the importance of tumor genetics to radiation response, this may represent a currently under-utilized means of enhancing treatment outcomes. In addition, recent studies have shown potentially actionable mutations in BM which are not present in the primary tumor. Overall, this suggests that further investigation into the pathways mediating radiation response variability is warranted. Here, we provide an overview of key mechanisms implicated in BM radiation resistance, including intrinsic and acquired resistance and intratumoral heterogeneity. We then discuss advances in tumor sampling methods, such as a collection of cell-free DNA and RNA, as well as progress in genomic analysis. We further consider how these tools may be applied to provide personalized radiotherapy for BM, including patient stratification, detection of radiotoxicity, and use of radiosensitization agents. In addition, we describe recent developments in preclinical models of BM and consider their relevance to investigating radiation response. Given the increase in clinical trials evaluating the combination of radiotherapy and targeted therapies, as well as the rising incidence of BM, it is essential to develop genomically informed approaches to enhance radiation response.

  View details for DOI 10.1038/s41420-024-02270-2

  View details for PubMedID 39695143

  View details for PubMedCentralID PMC11655559

• Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues. The Journal of clinical investigation Ali, A., Canaday, L. M., Feldman, H. A., Cevik, H., Moran, M. T., Rajaram, S., Lakes, N., Tuazon, J. A., Seelamneni, H., Krishnamurthy, D., Blass, E., Barouch, D. H., Waggoner, S. N. 2021; 131 (18)

  Abstract

  NK cell suppression of T cells is a key determinant of viral pathogenesis and vaccine efficacy. This process involves perforin-dependent elimination of activated CD4+ T cells during the first 3 days of infection. Although this mechanism requires cell-cell contact, NK cells and T cells typically reside in different compartments of lymphoid tissues at steady state. Here, we showed that NK cell suppression of T cells is associated with transient accumulation of NK cells within T cell-rich sites of the spleen during lymphocytic choriomeningitis virus infection. The chemokine receptor CXCR3 was required for this relocation and suppression of antiviral T cells. Accordingly, NK cell migration was mediated by type I IFN-dependent promotion of CXCR3 ligand expression. In contrast, adenoviral vectors that weakly induced type I IFN and did not stimulate NK cell inhibition of T cells also did not promote measurable redistribution of NK cells to T cell zones. Exogenous IFN rescued NK cell migration during adenoviral vector immunization. Thus, type I IFN and CXCR3 were critical for properly positioning NK cells to constrain antiviral T cell responses. Development of strategies to curtail migration of NK cells between lymphoid compartments may enhance vaccine-elicited immune responses.

  View details for DOI 10.1172/JCI146686

  View details for PubMedID 34314390

  View details for PubMedCentralID PMC8439606

• The Promise and Peril of Natural Killer Cell Therapies in Pulmonary Infection. Immunity Rajaram, S., Canaday, L. M., Ochayon, D. E., Rangel, K. M., Ali, A., Gyurova, I. E., Krishnamurthy, D., Fletcher, J. S., Reighard, S. D., Cox, A., Weirauch, M. T., Kottyan, L. C., Deshmukh, H., Zacharias, W. J., Borchers, M. T., Waggoner, S. N. 2020; 52 (6): 887-889

  View details for DOI 10.1016/j.immuni.2020.04.018

  View details for PubMedID 32405233

  View details for PubMedCentralID PMC7219410

• Moving in for the kill: natural killer cell immunoregulation requires CXCR3 Ali, A., Moran, M. T., Tuazon, J., Rajaram, S., Waggoner, S. N. AMER ASSOC IMMUNOLOGISTS. 2020

  View details for Web of Science ID 000589972401074

• A BAFF-ling new role for NK cells in promoting marginal zone antibacterial resistance during chronic virus infection Ali, A., Cranert, S. A., Moran, M. T., Rajaram, S., Waggoner, S. N. AMER ASSOC IMMUNOLOGISTS. 2020

  View details for Web of Science ID 000589972401066