Composition of the immune microenvironment differs between carcinomas metastatic to the lungs and primary lung carcinomas


Wijendra Senarathne, Semir Vranic, Joanne Xiu, Inga Rose, Peggy Gates, & Zoran Gatalicaa

Lungs are among the most common sites for development of both primary and metastatic carcinomas. Tumor cells expression (TC) of PD-L1 is an important predictor of the of response to immune check-point inhibition in NSCLC, while the composition of the immune cells (IC) in the tumor microenvironment including PD-L1+ cells is believed to predict responses in tumors of some other primary sites. Total mutational load (TML) and microsatellite instability (MSI) also play a role in response to the immune checkpoint blockade. We investigated immune microenvironment characteristics (PD-1, PD-L1, CD8) of 257 lung biopsies including 81 primary (NSCLC) and 176 metastatic tumors to the lungs. TML and MSI were calculated from massively parallel sequencing (592-gene panel). TC expression of PD-L1 was more common in NSCLC than in metastatic carcinomas (28% vs. 10%, p=0.009), while PD-L1-positive IC were present at relevant percentages (1–5%) exclusively in metastatic carcinomas (31% IC positive vs. 0%, p < 0.001). Metastatic carcinomas carried significantly lower TML in comparison with the NSCLCs (6.6 mutations on average vs. 10, p=0.01). All primary NSCLC were microsatellite stable, and only 2 metastatic carcinomas exhibited MSI-H status. The number of PD-1+ and CD8+ tumor infiltrating lymphocytes did not differ significantly between the primary and metastatic carcinomas. Our study revealed significant differences in tumor immune microenvironment (PD-L1 in IC and TC), and its relationship to TML between NSCLC and metastatic cancers. These differences could determine the choice of a predictive biomarker test and subsequently effect(s) of the immune therapy treatments in various advanced cancers.

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