Tumor Resident Memory T Cells: New Players in Immune Surveillance and Therapy.

Nina Dumauthioz,Sara Labiano,Pedro Romero

doi:10.3389/fimmu.2018.02076

Abstract

Tissue resident memory T cells (Trm) are a subset of memory T cells mainly described in inflammation and infection settings. Their location in peripheral tissues, such as lungs, gut, or skin, makes them the earliest T cell population to respond upon antigen recognition or under inflammatory conditions. The study of Trm cells in the field of cancer, and particularly in cancer immunotherapy, has recently gained considerable momentum. Different reports have shown that the vaccination route is critical to promote Trm generation in preclinical cancer models. Cancer vaccines administered directly at the mucosa, frequently result in enhanced Trm formation in mucosal cancers compared to vaccinations via intramuscular or subcutaneous routes. Moreover, the intratumoral presence of T cells expressing the integrin CD103 has been reported to strongly correlate with a favorable prognosis for cancer patients. In spite of recent progress, the full spectrum of Trm anti-tumoral functions still needs to be fully established, particularly in cancer patients, in different clinical contexts. In this mini-review we focus on the recent vaccination strategies aimed at generating Trm cells, as well as evidence supporting their association with patient survival in different cancer types. We believe that collectively, this information provides a strong rationale to target Trm for cancer immunotherapy.

Highlights

Tumor-infiltrating lymphocytes (TILs) frequently remain tolerant or display an exhausted phenotype favored by the tumor microenvironment [1,2,3]
In a glioblastoma preclinical model, the injection of tumor cells by distinct routes was shown to promote different patterns of integrins on specific T lymphocytes isolated from the respective tumor-draining lymph nodes [15]. These results suggest a mechanistic explanation of the impact of the immunization route in the generation of to consider resident memory cells (Trm) cells [16,17,18,19,20,21,22,23]
The growing interest in CD8+ Trm cells is illustrated in the number of recent studies aimed at understanding the optimal way to promote their formation in preclinical cancer models

Summary

Introduction

Tumor-infiltrating lymphocytes (TILs) frequently remain tolerant or display an exhausted phenotype favored by the tumor microenvironment [1,2,3]. In this mini-review we will cover two main aspects of Trm cells in cancer: the importance of the vaccination route to promote Trm cells against tumor antigens and the evidence substantiating an association of their occurrence to patient survival. In a model of cervicovaginal cancer, the generation of CD8 T cells with a resident phenotype was promoted upon intravaginal viral vector-based vaccination, which boosted circulating tumor-specific T cells.

Results

Conclusion