Bronchoalveolar lavage fluid reveals factors contributing to the efficacy of PD-1 blockade in lung cancer

Bronchoalveolar lavage is commonly performed to examine inflammation and responsible pathogens in lung diseases, and its findings may be used to assess the immune profile of the lung tumor microenvironment (TME). To investigate whether analyses of bronchoalveolar lavage fluid (BALF) can help identify non-small cell lung cancer (NSCLC) patients who respond to immune checkpoint inhibitors (ICIs), BALF and blood were prospectively collected before initiating nivolumab. The secreted molecules, microbiome, and cellular profiles based on BALF and blood analysis were compared regarding therapeutic effect in 12 patients. Compared to non-responders, responders showed significantly higher CXCL9 levels and greater diversity in the lung microbiome profile in BALF, and greater frequency of CD56+ subset in blood T cells, whereas no significant difference was found in PD-L1 expression of tumor cells. Antibiotic treatment in a preclinical lung cancer model significantly decreased CXCL9 in the lung TME, resulting in reduced sensitivity to nivolumab, which was reversed by CXCL9 induction in tumor cells. Thus, CXCL9 and the microbiome in the lung TME might be associated with each other, and their balance could contribute to nivolumab sensitivity in NSCLC patients. BALF analysis can help predict the efficacy of ICIs when performed along with currently approved examinations. The transcriptome profiles of bulk cells collected from BALF were compared between four responders and three non-responders.