LYG1 exerts antitumor function through promoting the activation, proliferation, and function of CD4⁺ T cells

Identification of novel stimulatory cytokines with antitumor function would have great value in tumor immunotherapy investigations. Here, we report LYG1 (Lysozyme G-like 1) identified through the strategy of Immunogenomics as a novel classical secretory protein with tumor-inhibiting function. LYG1 recombinant protein (rhLYG1) could significantly suppress the growth of B16 tumors in WT B6 mice, but not in SCID-beige mice, Rag1 mice, CD4⁺- or CD8⁺ T cell-deleted mice. It could increase the number of CD4⁺ and CD8⁺ T cells in tumor-infiltrating lymphocytes, tumor-draining lymph nodes, and spleens, and promote IFNγ production by T cells in tumor-bearing mice. In vitro experiments demonstrated that rhLYG1 could directly enhance IFNγ secretion by CD4⁺ T cells, but not CD8⁺ T cells. Moreover, it could promote the activation, proliferation, and IFNγ production of tumor antigen-specific CD4⁺ T cells. The tumor-inhibiting effect of LYG1 was eliminated in Ifng mice. Furthermore, LYG1 deficiency accelerated B16 and LLC1 tumor growth and inhibited the function of T cells. In summary, our findings reveal a tumor-inhibiting role for LYG1 through promoting the activation, proliferation, and function of CD4⁺ T cells in antitumor immune responses, offering implications for novel tumor immunotherapy.