Resident Memory T Cells in the Tumor Microenvironment
Tissue-resident memory T (TRM) cells are strategically positioned within the epithelial layers of many tissues to provide enduring site-specific immunological memory. This unique T-cell lineage is endowed with the capacity to rapidly respond to tissue per
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Resident Memory T Cells in the Tumor Microenvironment Jason B. Williams and Thomas S. Kupper
Abstract
Tissue-resident memory T (TRM) cells are strategically positioned within the epithelial layers of many tissues to provide enduring site-specific immunological memory. This unique T-cell lineage is endowed with the capacity to rapidly respond to tissue perturbations and has a well-documented role in eradicating pathogens upon reexposure. Emerging evidence has highlighted a key role for TRM cells in cancer immunity. Single-cell approaches have identified TRM cells among other CD8+ tumor-infiltrating lymphocyte (TIL) subsets, and their presence is a positive indicator of clinical outcome in cancer patients. Furthermore, recent preclinical studies have elegantly demonstrated that TRM cells are a critical component of the antitumor immune response. Given their unique functional abilities, TRM cells have emerged as a potential immunotherapeutic target. Here, we discuss TRM cells in the framework of the cancer-immunity cycle and in the context of the T cell- and non-T cell-inflamed tumor J. B. Williams · T. S. Kupper (*) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Boston, Harvard Medical School, Boston, MA, USA e-mail: [email protected]
microenvironments (TME). We highlight how their core features make TRM cells uniquely suited to function within the metabolically demanding TME. Finally, we consider potential therapeutic avenues that target TRM cells to augment the antitumor immune response. Keywords
Tissue-resident memory T cells · Cancer · Immunity · Microenvironment · Immune exclusion · T cell dysfunction · Antigen- presenting cells · Immunotherapy
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Introduction
While the immune response to cancer is incompletely understood, cytotoxic CD8+ T lymphocytes are thought to be the fundamental antitumor effector cells. The presence of a CD8+T-cell infiltrate is a positive prognostic marker in most types of solid cancer [1–3] and can predict clinical response to immune checkpoint blockade therapy [4, 5]. Most of these therapies aim to increase the frequency and function of tumor-infiltrating T lymphocytes (TILs) by inhibiting the negative regulatory pathways present in the tumor microenvironment (TME). Despite recent advances in immunotherapy to harness the power of these
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2020 A. Birbrair (ed.), Tumor Microenvironment, Advances in Experimental Medicine and Biology 1273, https://doi.org/10.1007/978-3-030-49270-0_3
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cells, cures remain rare, and only a subset of patients exhibit durable responses. At present, a fundamental objective in the field of immunotherapy is to understand the biological mechanisms behind the lack of clinical response and to develop new therapeutic approaches to overcome these obstacles. Research over the past 20 years has revealed a network of checkpoints impeding effective T cell-me
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