Nicolás Bastidas

All Publications

• Long-term Follow-up of Gastrointestinal CAR T-cell Lymphoma: Homing, Clonal Expansion, and Response to Cyclosporine. Blood Hosoya, H., Bastidas Torres, A. N., Fernandez-Pol, S., Gubatan, J. M., Najidh, S., Duran, G. E., Dong, F., Ehlinger, Z., Lohman, C., Wright, C., Sahaf, B., Mackall, C. L., Miklos, D. B., Sidana, S., Kurtz, D. M., Khodadoust, M. S., Mikkilineni, L. 2025

  Abstract

  CAR T-cell therapy has emerged as a transformative treatment for hematological malignancies, yet its potential to drive lymphomagenesis poses significant clinical concerns. In this study, we investigated the mechanisms underlying CAR T-cell-associated lymphomagenesis in the gastrointestinal (GI) tract on a single case, focusing specifically on the role of integrin a4b7 expression and a predisposing somatic SH2B3 mutation. We observed oligoclonal CAR T-cells homing to and clonally expanding in the GI tract, with the dominant expanded clone harboring both a pathogenic SH2B3 mutation and a CAR transgene integration within a TFCP2 locus. The clonal CAR T-cells subsequently transitioned beyond the GI tract into the peripheral blood, suggesting a potential pathway for systemic dissemination. We found clinical, histological, and molecular evidence demonstrating the efficacy of cyclosporine in reducing the expanded malignant clone and achieving durable clinical remission for more than a year. Our findings highlight the complex interplay between CAR T-cell therapy, pre-existing genetic vulnerabilities, and the GI microenvironment, emphasizing the need for vigilant monitoring and tailored therapeutic strategies to address the risks associated with CAR-T lymphomagenesis.

  View details for DOI 10.1182/blood.2025031423

  View details for PubMedID 41288531

• Genetic alteration of class I HLA in cutaneous T-cell lymphoma. Blood Kwang, A. C., Duran, G. E., Fernandez-Pol, S., Najidh, S., Li, S., Bastidas Torres, A. N., Wang, E. B., Herrera, M., Bandali, T. I., Kurtz, D. M., Kim, Y. H., Khodadoust, M. S. 2024

  Abstract

  Abnormalities involving class I HLA are frequent in many lymphoma subtypes but have not yet been extensively studied in cutaneous T-cell lymphomas (CTCL). We characterized the occurrence of class I HLA abnormalities in 65 patients with advanced mycosis fungoides (MF) or Sézary syndrome (SS). Targeted DNA sequencing including coverage of HLA loci revealed at least one HLA abnormality in 26/65 patients (40%). Twelve unique somatic HLA mutations were identified across nine patients, and loss of heterozygosity or biallelic loss of HLA was found to affect 24 patients. Although specific HLA alleles were commonly disrupted, these events did not associate with decreased total class I HLA expression. Genetic events preferentially disrupted HLA alleles capable of presentation of greater numbers of putative neoantigens. HLA abnormalities co-occurred with other genetic immune evasion events and were associated with worse progression-free survival. Single-cell analyses demonstrated HLA abnormalities were frequently subclonal. Through analysis of serial samples, we observed disrupting class I HLA events change dynamically over the disease course. The dynamics of HLA disruption are highlighted in a patient receiving pembrolizumab, where resistance to pembrolizumab was associated with elimination of an HLA mutation. Overall, our findings show that genomic class I HLA abnormalities are common in advanced CTCL and may be an important consideration in understanding the effects of immunotherapy in CTCL.

  View details for DOI 10.1182/blood.2024024817

  View details for PubMedID 39388712

• Multi-omic profiling reveals the endogenous and neoplastic responses to immunotherapies in cutaneous T cell lymphoma. Cell reports. Medicine Glass, D. R., Mayer-Blackwell, K., Ramchurren, N., Parks, K. R., Duran, G. E., Wright, A. K., Bastidas Torres, A. N., Islas, L., Kim, Y. H., Fling, S. P., Khodadoust, M. S., Newell, E. W. 2024: 101527

  Abstract

  Cutaneous T cell lymphomas (CTCLs) are skin cancers with poor survival rates and limited treatments. While immunotherapies have shown some efficacy, the immunological consequences of administering immune-activating agents to CTCL patients have not been systematically characterized. We apply a suite of high-dimensional technologies to investigate the local, cellular, and systemic responses in CTCL patients receiving either mono- or combination anti-PD-1 plus interferon-gamma (IFN-γ) therapy. Neoplastic T cells display no evidence of activation after immunotherapy. IFN-γ induces muted endogenous immunological responses, while anti-PD-1 elicits broader changes, including increased abundance of CLA+CD39+ T cells. We develop an unbiased multi-omic profiling approach enabling discovery of immune modules stratifying patients. We identify an enrichment of activated regulatory CLA+CD39+ T cells in non-responders and activated cytotoxic CLA+CD39+ T cells in leukemic patients. Our results provide insights into the effects of immunotherapy in CTCL patients and a generalizable framework for multi-omic analysis of clinical trials.

  View details for DOI 10.1016/j.xcrm.2024.101527

  View details for PubMedID 38670099

• Molecular advances in cutaneous T-cell lymphoma. Seminars in cutaneous medicine and surgery Bastidas Torres, A. N., Najidh, S., Tensen, C. P., Vermeer, M. H. 2018; 37 (1): 81-86

  Abstract

  Cutaneous T-cell lymphoma (CTCL) is a group of malignancies derived from skin-homing T cells. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common CTCL variants. In recent years, the genetic landscape of SS/MF has been characterized using genome-wide nextgeneration sequencing approaches. These studies have revealed that genes subjected to oncogenic mutations take part in cell cycle regulation, chromatin modification, Janus kinase (JAK)-signal transducer and activator of transcription protein (STAT) signaling, T-cell receptor (TCR)/ nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and microtubule associated protein kinase (MAPK) signaling, which suggests that deregulation of these cellular processes underlies lymphomagenesis. These studies provide the groundwork for functional and clinical studies that will lead to better risk assessment and more effective therapeutic approach in CTCL patients.

  View details for DOI 10.12788/j.sder.2018.007

  View details for PubMedID 29719024