Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells

Abstract

Background: There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. Methods: In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFNγ for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. Results: We discovered that IFNγ increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. Conclusions: Here we clarify for the first time an additional mechanism of anti-tumour effect—as exerted by anti-PD-1 antibody decreasing Treg— we anticipate that our findings will lead to the development of new methods for cancer treatment.

Advancements in osteosarcoma management: integrating immune microenvironment insights with immunotherapeutic strategies

“…Subsequent research has substantiated Tregs' role in facilitating tumor cell immune evasion. Notably, Yoshida et al reported that anti-PD-1 antibodies reduced Tregs infiltration in osteosarcoma, correlating with tumor growth delay and prolonged survival (Yoshida et al, 2020). Biller et al's research on canine osteosarcoma demonstrated an increase in Tregs and a concurrent reduction in the CD8 + T cells to Tregs proportion, correlating with diminished survival times, further emphasizing the importance of Tregs in facilitating tumor immune escape (Biller et al, 2010).…”

Identification of MAP3K15 as a potential prognostic biomarker and correlation with immune infiltrates in osteosarcoma

“…Recently, immunotherapy has made breakthroughs in the field of cancer therapy. Immune checkpoint inhibitors, such as PD-1, PD-L1, and CTAL4, have shown significant antitumor effects on various cancers (7)(8)(9). Additionally, these immune checkpoint inhibitors have been shown to play substantial roles in the treatment of OS.…”