Comparative study of the genomic landscape and tumor microenvironment among large cell carcinoma of the lung, large cell neuroendocrine of the lung, and small cell lung cancer

Deciphering the genomic profiles and tumor microenvironment (TME) in large cell carcinomas of the lung (LCC), large cell neuroendocrine of the lung (LCNEC), and small cell lung cancer (SCLC) might contribute to a better understanding of lung cancer and then improve outcomes. Ten LCC patients, 12 LCNEC patients, and 18 SCLC patients were enrolled. Targeted next-generation sequencing was used to investigate the genomic profiles of LCC, LCNEC, and SCLC. Tumor-infiltrating lymphocytes (TILs) within cancer cell nests and in cancer stroma were counted separately. Precise 60% of LCNEC patients harbored classical non-small cell lung cancer driver alterations, occurring in BRAF, KRAS, ROS1, and RET. More than 70% of SCLC patients harbored TP53-RB1 co-alterations. Moreover, 88.9%, 40%, and 77.8% of LCC, LCNEC, and SCLC cases had a high tumor mutation burden level with more than 7 mutations/Mb. Furthermore, high index of CD68(+) CD163(+) (TILs within cancer cell nests/ TILs within cancer cell nests and in cancer stroma, P = .041, 548 days vs not reached) and CD163(+) TILs (P = .041, 548 days vs not reached) predicted a shorter OS in SCLC. Our findings revealed the distinct genomic profiles and TME contexture among LCC, LCNEC, and SCLC. Our findings suggest that stratifying LCNEC/SCLC patients based on TME contexture might help clinical disease management.