The Potential of T Cell Factor 1 in Sustaining CD8+ T Lymphocyte-Directed Anti-Tumor Immunity

Abstract

T cell factor 1 (TCF1) is a transcription factor that has been highlighted to play a critical role in the promotion of T cell proliferation and maintenance of cell stemness in the embryonic and CD8+ T cell populations. The regulatory nature of TCF1 in CD8+ T cells is of great significance, especially within the context of T cell exhaustion, which is linked to the tumor and viral escape in pathological contexts. Indeed, inhibitory signals, such as programmed cell death 1 (PD-1) and cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4), expressed on exhausted T lymphocytes (TEX), have become major therapeutic targets in immune checkpoint blockade (ICB) therapy. The significance of TCF1 in the sustenance of CTL-mediated immunity against pathogens and tumors, as well as its recently observed necessity for an effective anti-tumor immune response in ICB therapy, presents TCF1 as a potentially significant biomarker and/or therapeutic target for overcoming CD8+ T cell exhaustion and resistance to ICB therapy. In this review, we aim to outline the recent findings on the role of TCF1 in T cell development and discuss its implications in anti-tumor immunity.

Decreased TCF1 and BCL11B expression predicts poor prognosis for patients with chronic lymphocytic leukemia

“…To further explore the mechanism by which TCF1 regulates CLL prognosis and the partner molecules interacting with TCF1, functional and pathway enrichment analysis revealed that TCF1 is positively correlated with BCL11B, which is mainly involved in T cell differentiation and activation and immune regulation in CLL patients, in accordance with the literature (20,22). Moreover, BCL11B was highly consistent with TCF1 in terms of decreased expression and the prediction of poor prognosis based on analysis of public datasets and HNCH data.…”

“…These findings indicated that BCL11B is highly correlated with TCF1 and coordinates with this gene to maintain the stem-like properties and cytotoxicity of effector CD8+ T cells (22,24,41). Unfortunately, we found that TCF1 and BCL11B expression was decreased in CLL patients, and this resulted in impaired differentiation potential for effector CD8+ T cells (21,22), which clinically manifested as the accumulation of terminally differentiated T cells (44), immune function dysfunction, and further rapid CLL progression. Although the data were not yet significant enough, this, to some extent, explains why decreased TCF1 and BCL11B expression leads to poor prognosis for patients with CLL.…”

“…Accumulating studies have illustrated that TCF1 is a key regulator for maintaining the stem-like properties of central memory CD8+ T cells and the cytotoxicity of effector CD8+ T cells (22,41). TCF1+CD8+ T cells reportedly serve as a positive biomarker for prolonged survival and effective response to anti-PD-1 treatment in solid tumors (24, 27).…”

“…Additionally, as pivotal T cell-specific transcription factors, TCF1 and BCL11B also participate in T cell activation and expansion (15,(18)(19)(20). More importantly, TCF1 and BCL11B are crucial for maintaining the stem-like properties of CD8+ T cells (21)(22)(23)(24). Upon stimulation, TCF1 promotes CD8+ T cells to differentiate into TCF1+CD8+ T cells that participate in effective antitumor immunity (24,25).…”

The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing

“…DNs subsequently express CD4 and CD8 upon the induction of the thymus microenvironment to become double-positive cells (DPs). 30 Then, DPs develop into single-positive T cells expressing the surface markers CD4 or CD8 through the action of a series of regulatory signals, such as protein arginine methyltransferase 5 31 and T cell factor 1 32 to coregulate the immune response. Therefore, T cells are often divided into CD4 + T cells or CD8 + T cells.…”