FOXP3+ regulatory T cells and the immune escape in solid tumours

Abstract

FOXP3+ regulatory T (Treg) cells play critical roles in establishing the immunosuppressive tumour microenvironment, which is achieved and dynamically maintained with the contribution of various stromal and immune cell subsets. However, the dynamics of non-lymphoid FOXP3+ Treg cells and the mutual regulation of Treg cells and other cell types in solid tumour microenvironment remains largely unclear. In this review, we summarize the latest findings on the dynamic connections and reciprocal regulations of non-lymphoid Treg cell subsets in accordance with well-established and new emerging hallmarks of cancer, especially on the immune escape of tumour cells in solid tumours. Our comprehension of the interplay between FOXP3+ Treg cells and key hallmarks of cancer may provide new insights into the development of next-generation engineered T cell-based immune treatments for solid tumours.

Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy

“…Regulatory T cells (Tregs), a class of immunosuppressive cells, are responsible for tumor cell immune escape. [ 37 , 38 ] Therefore, Treg infiltration in mouse tumors was further analyzed. The results showed that the proportion of Tregs in the mice treated with ES@CuO+PD‐1 was significantly lower than that in the control mice, while the proportion of CD3 + CD4 + T cells did not change among the groups (Figure S20 , Supporting Information).…”

FOXP3: A Player of Immunogenetic Architecture in Lung Cancer

“…It was shown that CTLA-4 is constitutively expressed on Treg cells [44]. FOXP3+ Treg cell-mediated immunosuppression is also implemented by the release of a variety immunosuppressive cytokines, e.g., IL-10, IL-35 and TGF-β [42,45]. The mechanisms described above demonstrate that FOXP3+ Treg cells promote immune escape from cancer.…”

“…The FOXP3+ Tregs are known for their immunosuppressive functions and their presence in the TME may suppress the anti-tumor immune response by the inhibition of the activity of cytotoxic T cells and other effector immune cells, contributing to immune evasion by the cancer cells [38,41] (Figure 3). The occurrence of an immunosuppressive TME promotes tumor growth and progression; for this reason, the FOXP3+ Tregs presence has been associated with a poor prognosis in various solid tumors [42], including NSCLC (HR: 3.91 and p < 0.001) [43]. In addition, among patients with node-negative NSCLC (N0), tumor-infiltrating FOXP3+ Tregs were positively correlated with intratumor COX-2 expression and were associated with a worse recurrence-free survival [10].…”

“…In addition, among patients with node-negative NSCLC (N0), tumor-infiltrating FOXP3+ Tregs were positively correlated with intratumor COX-2 expression and were associated with a worse recurrence-free survival [10]. Tumor-infiltrating Treg cells directly promote tumor immune evasion in multiple mechanisms [42]. The most important is the modulation of expression of checkpoint suppressor molecules, such as CTLA-4 [44], PD-1, TIM-3, LAG-3 and TIGIT [39,41,42] (Figure 2).…”

“…Tumor-infiltrating Treg cells directly promote tumor immune evasion in multiple mechanisms [42]. The most important is the modulation of expression of checkpoint suppressor molecules, such as CTLA-4 [44], PD-1, TIM-3, LAG-3 and TIGIT [39,41,42] (Figure 2). It was shown that CTLA-4 is constitutively expressed on Treg cells [44].…”