Phenotypic and functional characterization of tumor-reactive T cells in malignant pleural effusions
Year: 2026
Type: article
Abstract: Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) is effective for treating advanced melanoma but requires surgical tumor resection. Malignant pleural effusions (MPE) may provide a more accessible source of tumor-reactive T cells. Synchronously collected MPE, lung metastasis, and blood from a patient with metastatic melanoma were analyzed using high-dimensional flow cytometry, and single-cell RNA/T cell receptor (TCR) sequencing. TCR reactivity to autologous tumor was tested in vitro. The proliferative and cytotoxic capacity of ex vivo expanded T cells was assessed in vitro. MPE contained a higher fraction of CD3+ T cells compared with tumor and was enriched for effector CD8+ T cells and effector memory CD4+ T cells. Compared with TIL, MPE T cells exhibited lower features of T cell exhaustion and higher cytotoxicity signatures. The clonal repertoire of MPE and tumor highly overlapped, including 62.2% of predicted neoantigen-specific (NeoTCR) clonotypes. MHC class I-restricted reactivity was functionally confirmed in two of four selected NeoTCR clonotypes. MPE T cells demonstrated higher proliferative capacity under high-dose IL-2 expansion relative to TIL and achieved comparable MHC class I-dependent tumor killing. Overall, MPE contains polyclonal, tumor-reactive T cells with favorable functional features, supporting MPE as an accessible source for TIL therapy.
Source: Cancer Immunology Research
Institution: Yale University
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1487263742, G2543112641, G3571368501, G3968055098, G4462060839, G531061286, The antigen specificity of tumor-targeting T cells in non-small cell lung cancer, G5952224436, G604747472, G7827448794, G8315287662, High Performance Computing Instrumentation for the Yale Center for Genome Analysis, G9000071549, G9000078561, G9000092774, G9000179731, G9000370812, Effect of anti-TIGIT and anti-PD-1 on regulatory T cells and cancer cells in human glioblastoma, Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung Cancer, YALE CANCER CENTER CALABRESI IMMUNO-ONCOLOGY TRAINING PROGRAM, Cancer Center Support Grant
OpenAlex ID: W7212271136