Crucial immunological roles of the invasion front in innate and adaptive immunity in cervical cancer

Br J Cancer. 2024 Dec;131(11):1762-1774. doi: 10.1038/s41416-024-02877-3. Epub 2024 Oct 29.

Abstract

Background: The immunostimulatory actions of innate and adaptive immune responses play a crucial role in the cancer-immunity cycle. Although cervical cancer (CC) exhibits a high recurrence rate, the relation with lymphocytes in the tumor tissue have not been analyzed.

Methods: We analyzed NKT, NK, and T cells, not only in peripheral blood (PB), but also tumor tissue through histological analysis from 23 patients with CC collected before treatment. A correlation of them between PB and the tumor tissue were assessed.

Results: We detected functional NKT and NKG2Dhi NK cells and effector CD4+ Tregs in PB. In the tumor, we detected the infiltration of LAG-3+ TIM-3+ CD4+ and CD8+ T cells rather than NK cells particularly in the invasion front (IF) by fluorescent multiplex immunohistochemistry. The heatmap and correlation analysis revealed that LAG-3+ TIM-3+ CD8+ T cells are highly associated with CD69+ CD103- exhausted CD8+ T cells. We identified the statistical relationship between CD4+Tregs in PB and the number of LAG-3+ TIM-3+ CD4+ T cells in the IF, which may be related to recurrence in patients with CC.

Conclusions: LAG-3+ TIM-3+ T cells located in the IF may play a key role in regulation of the tumor immune microenvironment.

MeSH terms

  • Adaptive Immunity* / immunology
  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Hepatitis A Virus Cellular Receptor 2 / immunology
  • Humans
  • Immunity, Innate* / immunology
  • Killer Cells, Natural / immunology
  • Middle Aged
  • Natural Killer T-Cells / immunology
  • Neoplasm Invasiveness
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Microenvironment / immunology
  • Uterine Cervical Neoplasms* / immunology
  • Uterine Cervical Neoplasms* / pathology

Substances

  • Hepatitis A Virus Cellular Receptor 2
  • HAVCR2 protein, human