Molecular analysis of tumor-promoting CD8+ T cells in two-stage cutaneous chemical carcinogenesis

Area of Science:

• Immunology
• Cancer Biology
• Dermatology

Background:

• Tumor-infiltrating lymphocytes (TILs) play complex roles in cancer progression.
• CD8(+) T cells are typically associated with anti-tumor immunity, but their function can be altered within the tumor microenvironment.

Purpose of the Study:

• To characterize the molecular phenotype of T-pro cells, a subset of CD8(+) TILs.
• To understand the role of T-pro cells in experimental cutaneous carcinogenesis.
• To identify potential biomarkers for cancer immunotherapy and related inflammatory conditions.

Main Methods:

• Whole-genome expression analysis comparing T-pro cells with systemic CD8(+) T cells in tumor-bearing mice.
• Tricolor flow cytometry to confirm cell surface markers and cytokine production (IL-17).
• Time-course analysis of TILs from papillomas and carcinomas.

Main Results:

• T-pro cells exhibit a distinct T helper 17-like profile (RORgammat, IL-17A, IL-17F) with regulatory markers (FoxP3, IL-10, Tim-3) and epithelial growth factors.
• T-pro cells have reduced cytotoxic potential compared to systemic CD8(+) T cells.
• The T-pro phenotype is associated with malignant progression in skin cancer models.

Conclusions:

• T-pro cells contribute to skin carcinogenesis and possess a unique immunoregulatory and pro-tumorigenic profile.
• This molecular characterization provides a foundation for understanding inflammation's role in skin cancer.
• Findings may inform cancer immunotherapy strategies and are relevant to conditions like psoriasis involving CD8(+) IL-17(+) T cells.