CELL INTELLIGENCE · 肿瘤细胞治疗研究

Lnk is an adaptor protein that attenuates cytokine receptor signaling in hematopoietic and immune cells, but its role in the behavior of CD8 + T cells within solid tumors is not well defined. Using a murine melanoma model, we compared tumor growth and immune infiltration in Lnk-deficient mice and in wild-type controls and evaluated CD8 + T cell trafficking toward chemokine signals produced by melanoma cells. Lnk-deficient mice developed smaller tumors containing greater numbers of intratumoral CD8 + cytotoxic T cells. Tumor chemokine profiles, including high levels of interleukin-8 family signals such as CXCL2, were comparable between groups, yet CD8 + T cells lacking Lnk showed enhanced migration toward melanoma-derived cues ex vivo and accumulated more effectively within tumors in vivo . Pharmacologic inhibition of CXCR1/2 abolished this migratory advantage. Upon stimulation with interleukin-8 family chemokines, Lnk-deficient CD8 + T cells exhibited increased activation of STAT3 and ERK signaling pathways. Moreover, antisense-mediated downregulation of Lnk in wild-type T cells resulted in enhanced accumulation within melanoma tumors following adoptive transfer into wild-type hosts. These findings identify Lnk as a negative regulator of CXCR1/2-dependent trafficking of CD8 + T cells in melanoma and suggest that modulating this intracellular checkpoint may improve T cell trafficking into solid tumors and enhance the effectiveness of adoptive cellular immunotherapies.