High prevalence of tuberculosis (TB). is observed in China, and one of the etiological factors for lung cancer is TB. Our study was aimed to compare the differences of the tumor microenvironment (TME) based on tumor PD-L1 expression and CD3+/ CD4+/CD8+ T cells infiltration in patients with non-small cell lung cancer (NSCLC) who have ever/current suffered from TB to those lung cancer patients without TB.
Tumor samples from 69 patients with lung cancer who have ever/current suffered from TB were retrospectively collected at Zhejiang Cancer Hospital and Hangzhou Red Cross Hospital. The 21 samples of control group (lung cancer patients who never suffered from TB) is collected in Zhejiang Cancer Hospital. Tumoral PD-L1 expression (N = 68) and CD3+/CD4+/CD8+ T cells infiltration (N = 58) was determined by immunohistochemistry (IHC), based on which TME was categorized into different subtype. Proportion of four TME subtypes was determined, and overall survival with PD-L1 expression and TME was analyzed. The whole exon sequencing was used to detect the different immune gene landscape between 40 lung cancer patients who have ever/current/never suffered from TB.
Patients with TB had a decrease of infiltration of PD-L1 expression and CD8+ T cells into tumors. In addition, a different prognosis was observed in patients with active TB. The WES test showed a significant difference in TP53 mutation, tumor mutation burden, neoantigen and mutation signature in lung patients with or without TB. Lung patients with TB had unique driver genes such as C1QB, CDKN2A and signaling pathways. After analyzing in TIMER database, TP53,C1QB, CDKN2A are closely related to various immune cells in NSCLC.
NSCLC patients with TB exhibited lower PD-L1 and CD8+ expression level in TME and have different genomic landscape compare to lung cancer patients. Immunotherapy may have less effective in patients with active or latent TB and is prone to re-ignition of TB because of the reduced expression of PD-L1 and CD8+. Novel C1QB and CDKN2A targeted therapies may be the future direction of treatment for these patients with lung cancer and TB.
Zhejiang cancer hospital.
Has not received any funding.
All authors have declared no conflicts of interest.