The article “PSGL-1 Immune Checkpoint Inhibition for CD4+ T Cell Cancer Immunotherapy” by DeRogatis et al. (2021) explores the potential of inhibiting P-selectin glycoprotein ligand-1 (PSGL-1) as a new cancer therapeutic strategy. The research focuses on CD4+ T cells and highlights the role of PSGL-1 in regulating the immune system, particularly in cancer. DeRogatis et al. discuss cancer immunotherapies, particularly in the context of immunosuppressive T-cell suppression.
Although well-established PD-1 and CTLA-4 inhibitors have shown success, the paper suggests that PSGL-1, which plays a role in cell migration, could function as a negative regulator of CD4+ T cells in various disease states, including cancer. The authors propose that blocking the PSGL-1 channel on CD4+ T cells could eradicate tumors and represent a novel strategy for cancer therapy.
The paper describes the PSGL-1 in various T cell subsets, including CD4+ T cells, and its effects on T cell migration. The authors present preclinical studies using PSGL-1-deficient mice injected with melanoma cell lines. These mice increased effector CD4+ and CD8+ T cells and decreased PD-1 expression, improving melanoma tumor control. Studies show that PSGL-1 inhibition may prevent CD4+ T cell depletion and enhance helper functions, thereby affecting the anti-tumor response (Díaz-García et al., 2023).
An article by Hope et al. (2023) describes the role of PSGL-1 in T cells during infection, similar to DeRogatis et al. (2021), who expanded the investigation of PSGL-1 function in cancer, with a particular focus on CD4+ T cells. Both papers recognize the importance of PSGL-1 in regulating T-cell responses, but under specific conditions. The paper highlights the effects of PSGL-1 on CD4+ T cell-depleting pathways in the tumor microenvironment, suggesting that PSGL-1 inhibition may induce immunosuppression.
DeRogatis et al.’s findings showed improved tumor control in PSGL-1-deficient mice, accompanied by enhanced CD4+ and CD8+ T cell responses, consistent with the hypothesis that PSGL-1 acts as a negative regulator. The expression of PD corresponds to -1 on PSGL-1-deficient T cells. Reduced and improved effector functions are the potential benefits of targeting PSGL-1 in the immune response. This change may be important for cancer immunotherapy in the broader context of the immune system.
References
DeRogatis, J. M., Viramontes, K. M., Neubert, E. N., & Tinoco, R. (2021). PSGL-1 immune checkpoint inhibition for CD4+ T cell cancer immunotherapy. Frontiers in Immunology, 1.
Díaz-García, E., García-Sánchez, A., Alfaro, E., López-Fernández, C., Mañas, E., Cano-Pumarega, I., & Cubillos-Zapata, C. (2023). PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea. Frontiers in Immunology, 14.
Hope, J. L., Otero, D. C., Bae, E. A., Stairiker, C. J., Palete, A. B., Faso, H. A., & Bradley, L. M. (2023). PSGL-1 attenuates early TCR signaling to suppress CD8+ T cell progenitor differentiation and elicit terminal CD8+ T cell exhaustion. Cell Reports, 42(5), 1-27.