Galectin-7 reprograms skin carcinogenesis by fostering innate immune evasive programs

Area of Science:

• Dermatology
• Immunology
• Cancer Biology

Background:

• Non-melanoma skin cancer (NMSC) incidence is increasing due to UV exposure and immunosuppression.
• Mechanisms of NMSC development and its immune landscape are not fully understood.

Purpose of the Study:

• To investigate the role of galectin-7 (Gal-7) in NMSC development.
• To elucidate the molecular and immunological mechanisms by which Gal-7 influences skin carcinogenesis.

Main Methods:

• Utilized transgenic mice overexpressing Gal-7 (Tg46) and Gal-7 knockout mice (Lgals7-/-).
• Administered chemical carcinogens (DMBA and TPA) to induce skin tumors.
• Performed RNA sequencing, flow cytometry, and in vivo cell transfer experiments.
• Analyzed human NMSC biopsies for Gal-7 expression and associated molecular profiles.

Main Results:

• Gal-7 overexpression in keratinocytes increased papilloma formation in mice.
• Gal-7 promoted the infiltration of immunosuppressive monocytic myeloid cells into tumors.
• Gal-7 enhanced the immunosuppressive activity of myeloid cells by increasing IL-10 and TGF-β1 secretion.
• Human NMSC samples showed elevated LGALS7 mRNA, Gal-7 protein, CXCL1, and c-Met activation, correlating with myeloid signatures.

Conclusions:

• Galectin-7 plays a critical role in mediating skin carcinogenesis.
• Gal-7 facilitates NMSC development by modulating the tumor immune microenvironment.
• Gal-7 represents a potential therapeutic target for human non-melanoma skin cancer.