![]() Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes. The ambiguous role of γδ t lymphocytes in antitumor immunity. This article presents a critical view of the impact of tumour-infiltrating γδT cells on clinical outcomes.Ĭhitadze, G., Oberg, H. Assessment of tumor-infiltrating TCR Vγ9Vδ2 γδ lymphocyte abundance by deconvolution of human cancers microarrays. Recommended to be read in combination with Deniger et al. This is an excellent but also controversial unbiased description of the immunological landscape of tumour-infiltrating lymphocytes that puts γδT cells at the centre of attention. The prognostic landscape of genes and infiltrating immune cells across human cancers. γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer. Distinctive features of tumor-infiltrating γδ T lymphocytes in human colorectal cancer. Tumor-infiltrating γδT cells predict prognosis and adjuvant chemotherapeutic benefit in patients with gastric cancer. Analysis of Vδ1 T cells in clinical grade melanoma-infiltrating lymphocytes. Cancer immunosurveillance by tissue-resident innate lymphoid cells and innate-like T cells. Contribution of IL-17-producing γ δ T cells to the efficacy of anticancer chemotherapy. Regulation of cutaneous malignancy by γδ T cells. Gammadelta T cells: first line of defense and beyond. In this Review, we discuss the challenges and opportunities for the clinical implementation of cancer immunotherapies based on γδT cells and their receptors.Ĭhien, Y. However, the precise mechanisms of tumour-specific γδT cells, as well as the mechanisms for self-recognition, remain poorly understood. Overall, γδT cells display potent cytotoxicity, which usually does not depend on tumour-associated (neo)antigens, towards a large array of haematological and solid tumours, while preserving normal tissues. Consequently, there is renewed interest among translational researchers and commercial partners in the therapeutic use of γδT cells and their receptors. Approaches that could address this limitation by engineering αβT cells, such as chimeric antigen receptor T (CAR T) cells, are being investigated intensively, but these approaches have other issues, such as a scarcity of appropriate targets for CAR T cells in solid tumours. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Clinical responses to checkpoint inhibitors used for cancer immunotherapy seemingly require the presence of αβT cells that recognize tumour neoantigens, and are therefore primarily restricted to tumours with high mutational load. ![]() Monitoring of the peripheral TCR and BCR repertoires may serve as a surrogate marker for the early detection of EGFR/ALK wild-type NSCLC patients who would benefit from anti-PD-1 treatment.Īnti-PD-1 antibody B cell receptor (BCR) repertoire EGFR/ALK Non-small cell lung cancer (NSCLC) T cell receptor (TCR) repertoire. These findings suggest the clinical significance of changes in peripheral TCR and BCR repertoire diversity after anti-PD-1 treatment in patients with NSCLC without EGFR/ALK mutation. Patients with more reduced TCR diversity showed better progression-free survival (PFS) in the EGFR/ALK wild-type subset (P = 0.011) but not in the mutant subset. The post-treatment reduction in TCR and BCR repertoire diversity was also significantly associated with the occurrence of adverse events in the EGFR/ALK wild-type subset (P = 0.022 and P = 0.014, respectively). Compared to non-responders (SD or PD), responders (PR) showed significantly decreased TCR and BCR diversity after treatment in the EGFR/ALK wild-type subset (P = 0.0014 and P = 0.034, respectively), but not in all the enrolled patients. TCR and BCR diversity was significantly correlated at baseline (R = 0.65 P = 1.6 × 10 -4) and on treatment (R = 0.72 P = 1.2 × 10 -5). The clinical significance of TCR and BCR repertoire diversity in peripheral blood was evaluated in all the enrolled patients (n = 30) or in the subset with (n = 10) or without (n = 20) EGFR/ALK mutation. Thus, analysis of TCR and BCR repertoires might help predict the clinical efficacy of anti-PD-1 treatment.īlood samples from 30 patients with non-small cell lung cancer (NSCLC) treated with anti-PD-1 antibody were collected before and six weeks after treatment initiation. TCR and BCR repertoire diversity plays a critical role in tumor immunity. ![]()
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