Regulation of regulatory T cells in cancer

Abstract

Summary The inflammatory response to transformed cells forms the cornerstone of natural or therapeutically induced protective immunity to cancer. Regulatory T (Treg) cells are known for their critical role in suppressing inflammation, and therefore can antagonize effective anti‐cancer immune responses. As such, Treg cells can play detrimental roles in tumour progression and in the response to both conventional and immune‐based cancer therapies. Recent advances in our understanding of Treg cells reveal complex niche‐specific regulatory programmes and functions, which are likely to extrapolate to cancer. The regulation of Treg cells is reliant on upstream cues from haematopoietic and non‐immune cells, which dictates their genetic, epigenetic and downstream functional programmes. In this review we will discuss how Treg cells are themselves regulated in normal and transformed tissues, and the implications of this cross talk on tumour growth.

Regulatory T cells in cancer: where are we now?

“…Frequency of Treg cells in the tumour immune infiltrate often far exceeds that in normal tissues, suggesting that co-option of Treg cells by tumours is an important feature of cancer development and a requisite for cancer progression in a number of tumour types. Stockis et al 27 consider the mechanisms that drive Treg cell accumulation within tumours, reviewing our understanding of the molecular basis for recruitment and maintenance of Treg cells within tumours, and proposing that selective recruitment of thymic Treg cells rather than de novo induction of induced Treg cells is the dominant mechanism by which Treg cells accumulate in cancer. While experimental observations supportive of this conclusion are presented, the relative functional contribution of thymic Treg and induced Treg cells to tumour immunosuppression has yet to be formally established.…”

Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer

“…Treg cells are critical in suppressing inflammation and can play detrimental roles in promoting tumor progression. 29 The ratio of FOXP3 + T cells to CD3 or CD8 + T cells is negatively correlated with multiple cancer survival. [30][31][32][33][34] Treg cells regulate immune system by suppressing the function of conventional T (Tconv) cells including CD4 + and CD8 + T cells, as well as dendritic cells (DCs), B cells, macrophages, mast cells and other cells.…”

Blocking inflammation to improve immunotherapy of advanced cancer

“…described an attempt to improve immune checkpoint inhibitor therapy by reprogramming Treg cells towards the synthesis of IFN‐ γ . This cytokine, together with IL‐2, is normally inhibited by Treg cells and is typically synthesized by Tconv cells to promote lymphocyte growth, proliferation and cytotoxicity . Interferon‐ γ also promotes expression of major histocompatibility complex class II (MHC II) on macrophages, thus increasing their antigen‐presenting capacity.…”

“…This cytokine, together with IL-2, is normally inhibited by Treg cells and is typically synthesized by Tconv cells to promote lymphocyte growth, proliferation and cytotoxicity. 30 Interferon-c also promotes expression of major histocompatibility complex class II (MHC II) on macrophages, thus increasing their antigen-presenting capacity. At the same time, IFN-c induces MHC I expression on neoplastic cells, improving targeting by cytotoxic T cells.…”