Sex difference in the expression of PD-1 of non-small cell lung cancer

Front Immunol. 2022 Oct 20:13:1026214. doi: 10.3389/fimmu.2022.1026214. eCollection 2022.

Abstract

Evidence increasingly indicated that lung cancer incidence in female individuals continue to rise, and women have a higher risk to develop adenocarcinoma than men. Male and female individuals differ in their innate and adaptive immune responses, and there are sex differences in response to the PD-1/PD-L1-dependent blocking immunotherapy. Whether the differential expression of PD-1 between genders affect the response to blocking treatment is currently unknown. In this study, we examined sex differences in serum sPD-1, mPD-1 expression on T cells, and sex hormone levels in non-small cell lung cancer (NSCLC) patients. Our results revealed a higher level of sPD-1 and expression of PD-1 on CD4+T cell in female patients than in male patients; we identified that serum sPD-1 level and the expression of mPD-1 on T cells were significantly reduced in NSCLC; we also found that serum testosterone level increased in female patients compared with control subjects and that increased testosterone downregulated the expression of mPD-1 on T cell. These findings provide a better understanding of the differences in PD-1 expression between genders in NSCLC patients and the effect of sex hormones on PD-1 expression and supply evidence for early lung cancer diagnosis and responsiveness to immune checkpoint inhibitors.

Keywords: NSCLC; immunotherapy; membrane PD-1 expression; sex difference; soluble PD-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung*
  • Female
  • Humans
  • Lung Neoplasms*
  • Male
  • Programmed Cell Death 1 Receptor / metabolism
  • Sex Characteristics
  • Testosterone

Substances

  • Programmed Cell Death 1 Receptor
  • Testosterone