Luciferase Reporter Cell Line - KLN205

Lung cancer is one of the most common malignancies in humans and a leading cause of death. Various therapies aimed at enhancing anti-tumor immune responses-including anti-programmed cell death protein 1 (anti-PD-1) antibodies-have been successfully applied in the treatment of numerous oncological diseases, such as non-small cell lung cancer (NSCLC). However, the host immune mechanisms mediating the efficacy of anti-PD-1 therapy have not yet been fully elucidated. Here, researchers discovered that anti-PD-1 therapy induces the generation of a population of circulating follicular helper T cells (cTfh) with enhanced B-cell activation capabilities, and that these cells participate in the tumor's response to treatment. Furthermore, anti-PD-1 treatment increases the abundance of tertiary lymphoid structures (TLS) within the tumor microenvironment, and this increase in TLS correlates positively with the suppression of tumor growth. Notably, TLS are capable of supporting local antibody production mediated by cTfh, thereby contributing to the host's immune response against the tumor.

To assess the impact of anti-PD-1 therapy on the anti-tumor immune response in our model, researchers first analyzed the immune cell profiles in the peripheral blood, secondary lymphoid organs (SLOs), and tumor-infiltrating lymphocytes (TILs) of tumor-bearing mice treated with either anti-PD-1 antibodies or isotype control antibodies. To this end, they subcutaneously inoculated DBA/2JRj mice with syngeneic non-small cell lung cancer (NSCLC) KLN205-Luc cells. Mice treated with the control antibody exhibited progressive tumor growth, whereas those treated with anti-PD-1 showed significant inhibition of tumor growth (Figure 1A). The researchers analyzed the distribution of immune cell subsets in both groups. The results revealed a significant increase in the number of cTfh cells (specifically, CD4+PD-1+CXCR5+ cells) in the peripheral blood of mice treated with anti-PD-1 antibodies. This increase was not observed in SLOs, which had comparable Tfh levels in both anti-PD-1-treated and isotype-treated mice (Figures 1B and 1C). The researchers performed staining analyses for CD25 and FoxP3 on Tfh cells in both the peripheral blood and the spleen. The results indicated that, in the peripheral blood, the ratio of follicular regulatory T cells (Tfr) to Tfh cells was significantly lower in mice treated with anti-PD-1 antibodies compared to those treated with isotype control antibodies; however, this change was not observed in the spleen. This finding ruled out the possibility that anti-PD-1 therapy simultaneously induces an increase in Tfr cells (Figure 1F).

Figure 1. Antiprogrammed cell death protein 1 (anti-PD-1) treatment induces circulating T follicular helper cells (cTfh) in non-small cell lung cancer (NSCLC)-bearing mice. (Sánchez-Alonso S, et al., 2020)