Cancer Immunol Res. 2025 Aug 8:OF1-OF2. doi: 10.1158/2326-6066.CIR-25-0624. Online ahead of print.
ABSTRACT
Anaplastic lymphoma kinase-rearranged lung adenocarcinoma (ALK+ LUAD) is currently considered an immune-resistant disease, yet underlying biological mechanisms are largely unknown. In this issue, Arai and colleagues analyzed the tumor microenvironment (TME) in ALK+ LUADs, identifying a myeloid cell-dominant immunosuppressive TME, primarily driven by IL6 secretion. Dual anti-IL6R/anti-PD-L1 treatment resulted in robust antitumor effect in mouse models, restoring immune sensitivity and tumor control. These findings highlight a promising therapeutic approach to enhance the efficacy of PD-(L)1 inhibitors by reverting TME-mediated immune resistance, reshaping the role of immunotherapy in ALK+ LUADs. See related article by Arai et al., p. XX .
PMID:40778656 | DOI:10.1158/2326-6066.CIR-25-0624