Dataset Information

Analysis of V?1 T cells in clinical grade melanoma-infiltrating lymphocytes.

ABSTRACT: ?? T cells, including V?1 and V?2 T cells, can recognize tumor-associated ligands neglected by conventional ?? T cells in a MHC-independent manner. Little is known regarding the anticancer potential and the possibility to isolate and expand V?1 T cells to therapeutically relevant numbers. In this study, we have detected low frequencies of V?1 T cells among tumor-infiltrating lymphocyte (TIL) products for adoptive cell transfer generated from melanoma metastases. An increased frequency of V?1 T cells was found among the cell products from patients with an advanced disease stage. V?1 T cells displayed in vitro antitumor activities and sufficient proliferative potential to generate over 1 × 10(9) cells using current protocols for T cell transfer. Infusion of V?1 T cells together with high numbers of ?? TILs in a clinical trial was safe and well tolerated. These data suggest that V?1 T cells should be further scrutinized as a potentially useful tool for the treatment of patients with metastatic melanoma.

SUBMITTER: Donia M

PROVIDER: S-EPMC3518502 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Analysis of Vδ1 T cells in clinical grade melanoma-infiltrating lymphocytes.

Donia Marco M Ellebaek Eva E Andersen Mads Hald MH Straten Per Thor PT Svane Inge Marie IM

Oncoimmunology 20121101 8

γδ T cells, including Vδ1 and Vδ2 T cells, can recognize tumor-associated ligands neglected by conventional αβ T cells in a MHC-independent manner. Little is known regarding the anticancer potential and the possibility to isolate and expand Vδ1 T cells to therapeutically relevant numbers. In this study, we have detected low frequencies of Vδ1 T cells among tumor-infiltrating lymphocyte (TIL) products for adoptive cell transfer generated from melanoma metastases. An increased frequency of Vδ1 T c ...[more]

PMID: 23243593

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Project description:Background: Human intratumoral T cell infiltrates can be defined by quantitative or qualitative features, such as their ability to recognize autologous tumor antigens. In this study, we reproduced the tumor-T cell interactions of individual patients to determine and compared the qualitative characteristics of intratumoral T cell infiltrates across multiple tumor types. Methods: We employed 187 pairs of unselected tumor-infiltrating lymphocytes (TILs) and autologous tumor cells from patients with melanoma, renal-, ovarian-cancer or sarcoma, and single-cell RNA sequencing data from a pooled cohort of 93 patients with melanoma or epithelial cancers. Measures of TIL quality including the proportion of tumor-reactive CD8+ and CD4+ TILs, and TIL response polyfunctionality were determined. Results: Tumor-specific CD8+ and CD4+ TIL responses were detected in over half of the patients in vitro, and greater CD8+ TIL responses were observed in melanoma, regardless of previous anti-PD-1 treatment, compared to renal cancer, ovarian cancer and sarcoma. The proportion of tumor-reactive CD4+ TILs was on average lower and the differences less pronounced across tumor types. Overall, the proportion of tumor-reactive TILs in vitro was remarkably low, implying a high fraction of TILs to be bystanders, and highly variable within the same tumor type. In situ analyses, based on eight single-cell RNA-sequencing datasets encompassing melanoma and five epithelial cancers types, corroborated the results obtained in vitro. Strikingly, no strong correlation between the proportion of CD8+ and CD4+ tumor-reactive TILs was detected, suggesting the accumulation of these responses in the tumor microenvironment to follow non-overlapping biological pathways. Additionally, no strong correlation between TIL responses and tumor mutational burden (TMB) in melanoma was observed, indicating that TMB was not a major driving force of response. No substantial differences in polyfunctionality across tumor types were observed. Conclusions: These analyses shed light on the functional features defining the quality of TIL infiltrates in cancer. A significant proportion of TILs across tumor types, especially non-melanoma, are bystander T cells. These results highlight the need to develop strategies focused on the tumor-reactive TIL subpopulation.

Dataset Information

Analysis of V?1 T cells in clinical grade melanoma-infiltrating lymphocytes.

Publications

Analysis of Vδ1 T cells in clinical grade melanoma-infiltrating lymphocytes.

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