Targeting Treg cells in cancer immunotherapy

Abstract

Foxp3‐expressing regulatory T (Treg) cells, which are indispensable for preventing autoimmunity, also suppress effective tumor immunity. Treg cells abundantly infiltrate into tumor tissues, which is often associated with poor prognosis in cancer patients. Removal of Treg cells enhances anti‐tumor immune responses but may also elicit autoimmunity. A key issue in devising Treg‐targeting cancer immunotherapy is, therefore, how to specifically deplete Treg cells infiltrating into tumor tissues without affecting tumor‐reactive effector T cells, while suppressing autoimmunity. This can be achieved by differentially controlling Treg and effector T cells by various ways. In this review, we discuss how tumor‐infiltrating Foxp3+ Treg cells hamper effective anti‐tumor immune responses especially in tumor tissues and how they can be specifically targeted for augmenting tumor immunity but not autoimmunity.

Heterogeneity and targeted therapy-induced adaptations in lung cancer revealed by longitudinal single-cell RNA sequencing

“…Increased pro-inflammatory chemokines Immune system modulation (Tokunaga et,al., 2018) 9 Increased Tregs Immune system modulation (Tanaka and,Sakaguchi, 2019) 10 Kyurenine signature Targeted inhibition and immune modulation (Labadie et al, 2019) (Chomienne et al, 1990). If deployed at the appropriate time, treatments that target liabilities of a specific cell state or prevent further adaptation may help improve patient survival by constraining continued tumor evolution towards complete drug resistance.…”

Bystander CD4+T cells infiltrate human tumors and are phenotypically distinct

“…Notably, because of their ability to directly kill tumor cells and a better knowledge of MHC class I tumor antigens, much more attention has been dedicated to the role of CD8 + T cells (37)(38)(39). In the meantime, many studies have also elucidated the detrimental role of CD4 + Treg cells in antitumor immunity and put these cells at the center stage as immunotherapy targets (40). Our work brings to light that consistently large fractions of total T cells infiltrating the tumor are made up of non-Treg CD4 + T cells in both colorectal and lung cancer.…”

Cancer Cell‐targeted and Activatable Photoimmunotherapy Spares T Cells in a 3D Coculture Model

“…As ICIs have not generally been successful on their own due to a number of immunological and physiological challenges, combination treatments that perturb the TIME from cold to hot are appealing . The advantage of taPIT over conventional modalities is the potential to more precisely modulate the TIME through specific targeting of cancer and immunosuppressive tumor cell subtypes including tumor‐associated macrophages , fibroblasts and regulatory T cells . Although the in vitro model in this work overestimates clinical measurements of E:T ratios in ovarian cancer , sparing local cytotoxic T cells may prove critical in future taPIT–ICI treatment strategies that facilitate a robust immune response after photodynamic destruction.…”

“…As ICIs have not generally been successful on their own due to a number of immunological and physiological challenges, combination treatments that perturb the TIME from cold to hot are appealing (47). The advantage of taPIT over conventional modalities is the potential to more precisely modulate the TIME through specific targeting of cancer and immunosuppressive tumor cell subtypes including tumor-associated macrophages (48,49), fibroblasts (25,50) and regulatory T cells (24,51).…”