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Understanding and dissecting the role of different subsets of regulatory tumor-infiltrating lymphocytes (TILs) in the immunopathogenesis of individual cancer is a challenge for anti-tumor immunotherapy. High levels of γδ regulatory T cells have been discovered in breast TILs. However, the clinical relevance of these intratumoral 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. Intratumoral 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 and overall survival of breast cancer patients. Multivariate and univariate analyses of tumor-infiltrating γδ T cells and other prognostic factors further suggested that intratumoral γδ T cells represented the most significant independent prognostic factor for assessing severity of breast cancer compared with the other known factors. Intratumoral 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 intratumoral γδ T cells may serve as a valuable and independent prognostic biomarker, as well as a potential therapeutic target for human breast cancer.

Breast cancer is the second leading cause of cancer-related deaths in women worldwide. Increasing evidence suggests that immunotherapy is a promising strategy for treating breast cancer, and understanding of the roles of different subtypes of tumor-infiltrating lymphocytes (TILs) in the tumor immunosuppressive microenvironment may be essential to cancer treatment and elimination. We recently discovered that enriched gammadelta1 T cell populations in the breast cancer TILs can suppress naïve and effector T cell responses and block the maturation and activities of dendritic cells (DC). In order to investigate the functional role of tumor-infiltrating gammadelta T cells in the immune pathogenesis of breast cancer, we further performed immunohistochemical staining to analyze gammadelta T cells, as well as CD4+, CD8+, IL-17-producing and FoxP3+ T cells in 50 freshly frozen tumor tissues from different stages of identified primary breast cancer and paired normal breast tissues. We found that the numbers of gammadelta T cells among tumor tissues were significantly increased compared with those in normal breast tissues in breast cancer patients. High numbers of gammadelta T cells were present in the patients with high tumor grades and lymph node metastases. Importantly, the patients with a high proportion of gammadelta T cells showed poorer survival rates in comparison to those with a low proportion of gammadelta T cells in breast cancer. These results indicate that gammadelta T cells constitute a dominant population existing in the breast tumor suppressive microenvironment that is negatively associated with clinical outcome, which may be an important cancer immunotherapeutic target for breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3544. doi:1538-7445.AM2012-3544