Alterations in Peripheral Lymphocyte Subsets under Immunochemotherapy in Stage IV SCLC Patients: Th17 Cells as Potential Early Predictive Biomarker for Response

Int J Mol Sci. 2024 May 7;25(10):5056. doi: 10.3390/ijms25105056.

Abstract

UICC stage IV small-cell lung cancer (SCLC) is a highly aggressive malignancy without curative treatment options. Several randomized trials have demonstrated improved survival rates through the addition of checkpoint inhibitors to first-line platin-based chemotherapy. Consequently, a combination of chemo- and immunotherapy has become standard palliative treatment. However, no reliable predictive biomarkers for treatment response exist. Neither PD-L1 expression nor tumor mutational burden have proven to be effective predictive biomarkers. In this study, we compared the cellular immune statuses of SCLC patients to a healthy control cohort and investigated changes in peripheral blood B, T, and NK lymphocytes, as well as several of their respective subsets, during treatment with immunochemotherapy (ICT) using flow cytometry. Our findings revealed a significant decrease in B cells, while T cells showed a trend to increase throughout ICT. Notably, high levels of exhausted CD4+ and CD8+ cells, alongside NK subsets, increased significantly during treatment. Furthermore, we correlated decreases/increases in subsets after two cycles of ICT with survival. Specifically, a decrease in Th17 cells indicated a better overall survival. Based on these findings, we suggest conducting further investigation into Th17 cells as a potential early predictive biomarkers for response in patients receiving palliative ICT for stage IV SCLC.

Keywords: Th 17 cells; cellular immune status; immunochemotherapy; predictive biomarker; small-cell lung cancer.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Female
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Small Cell Lung Carcinoma* / drug therapy
  • Small Cell Lung Carcinoma* / immunology
  • Small Cell Lung Carcinoma* / pathology
  • Th17 Cells* / immunology
  • Th17 Cells* / metabolism

Substances

  • Biomarkers, Tumor

Grants and funding

This research received no external funding.