Authors
Yael Derdikman Ofir, Miran Aswad, Michal Hayun, Antonina Pechkovsky, Ghazal Kheshaiboun, Narmeen Ghanayiem, Yasmine Khier, Yaniv Zohar, Yishai Ofran, Igal Louria-Hayon
Published in
Molecular therapy. Oncology. Volume 34. Issue 3. Pages 201288. Sep 17, 2026. Epub Jul 01, 2026.
Abstract
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.
PMID:
42519390
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.
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