Tumor-Infiltrating γδ T Lymphocytes Predict Clinical Outcome in Human Breast Cancer

Abstract

Understanding and dissecting the role of different subsets of regulatory tumor-infiltrating T lymphocytes (TILs) in the immunopathogenesis of individual cancer is a challenge for anti-tumor immunotherapy. High levels of γδ regulatory T (Treg) cells have been discovered in the breast TILs. However, the clinical relevance of these intra-tumoral γδ T cells is unknown. In this study, γδ T cell populations were analyzed by performing immunohistochemical staining in primary breast cancer tissues from patients with different stages of cancer progression. Retrospective multivariate analyses of the correlations between γδ T cell levels and other prognostic factors and clinical outcomes were completed. We found that γδ T cell infiltration and accumulation in breast tumor sites was a general feature in breast cancer patients. Intra-tumoral γδ T cell numbers were positively correlated with advanced tumor stages, HER2 expression status and high lymph node metastasis, but inversely correlated with relapse-free survival (RFS) and overall survival (OS) of breast cancer patients. Multivariate and univariate analyses of tumor-infiltrating γδ T cells and other prognostic factors further suggested that intra-tumoral γδ T cells were the most significant independent prognostic factor for assessing severity of breast cancer, compared with the other known factors. Intra-tumoral γδ T cells were positively correlated with FoxP3+ cells and CD4+ T cells, but negatively correlated with CD8+ T cells in breast cancer tissues. These findings suggest that intra-tumoral γδ T cells may serve as a valuable and independent prognostic biomarker, as well as a potential therapeutic target for human breast cancer.

Protective Role of the Inflammatory CCR2/CCL2 Chemokine Pathway through Recruitment of Type 1 Cytotoxic γδ T Lymphocytes to Tumor Beds

“…Moreover, Vd1 cells were the dominant tumor-infiltrating T cell population found in a collection of 74 primary cutaneous melanomas (19). However, other studies by Peng and colleagues (18) detected poor infiltration of Vd1 T cells, as well as total gd T cells (50), in melanoma biopsy specimens. By contrast, gd T cells, and Vd1 cells in particular, were abundant in breast and prostate tumors.…”

Murine CD27 (−) Vγ6 (+) γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages

“…In fact, γδ T cells represented the most significant independent prognostic factor for assessing severity of breast cancer (16). Similarly, a recent report on colorectal cancer showed a positive correlation between clinopathological parameters and the infiltration of γδ T cells specifically producing interleukin-17 (IL-17) (17).…”

“…Despite these highly promising reports, a clinical study on breast cancer tissue revealed a surprising inverse correlation between infiltrating γδ T cells and overall patient survival (16). In fact, γδ T cells represented the most significant independent prognostic factor for assessing severity of breast cancer (16).…”

Selective, efficient modulation of activated CD4+ αβT cells by the novel humanized antibody GZ-αβTCR targeting human αβTCR

“…47 Their continuance is of specific significance early after haematopoietic SCT when patients, still immunocompromised, suffer from a high risk of lymphoproliferative disorders 48 and relapse of the underlaying disease, as γδT cells can suppress B-cell expansion, 49 regulate T-cell leukaemia and exert potent antitumoural activity. [50][51][52][53][54][55][56] Furthermore, the key role of γδT cells in primary immune responses is undisputed in CMV, HSV-1 and Candida albicans infections, pathogens that are frequent after transplantation. [57][58][59] In addition, γδT cells are crucial modulators of immune responses and decisive in the induction and maintenance of tolerance in various physiological settings [60][61][62][63] and can directly promote allograft survival.…”