Abstract
The immune cells in the local environments surrounding non-small cell lung cancer (NSCLC) implicate the balance of pro- and antitumor immunity; however, their transcriptomic profiles remain poorly understood. A transcriptomic microarray study of bronchoalveolar lavage (BAL) cells harvested from tumor-bearing lung segments was performed in a discovery group. The findings were validated (1) in published microarray datasets, (2) in an independent group by RT-qPCR, and (3) in non-diseased and tumor adjacent non-neoplastic lung tissue by immunohistochemistry and in BAL cell lysates by immunoblotting. The differential expression of 129 genes was identified in the discovery group. These genes revealed functional enrichment in Fc gamma receptor-dependent phagocytosis and circulating immunoglobulin complex among others. Microarray datasets analysis (n = 607) showed that gene expression of BAL cells of tumor-bearing lung segment was also the unique transcriptomic profile of tumor adjacent non-neoplastic lung of early stage NSCLC and a significantly gradient increase of immunoglobulin genes' expression for non-diseased lungs, tumor adjacent non-neoplastic lungs, and tumors was identified (ANOVA, p < 2 × 10-16). A 53-gene signature was determined with significant correlation with inhibitory checkpoint PDCD1 (r = 0.59, p = 0.0078) among others, where the nine top genes including IGJ and IGKC were RT-qPCR validated with high diagnostic performance (AUC: 0.920, 95% CI: 0.831-0.985, p = 2.98 × 10-7). Increased staining and expression of IGKC revealed by immunohistochemistry and immunoblotting in tumor adjacent non-neoplastic lung tissues (Wilcoxon signed-rank test, p < 0.001) and in BAL cell lysates (p < 0.01) of NSCLC, respectively, were noted. The BAL cells of tumor-bearing lung segments and tumor adjacent non-neoplastic lung tissues present a unique gene expression characterized by IGKC in relation to inhibitory checkpoints. Further study of humoral immune responses to NSCLC is warranted.
Highlights
Novel immunotherapies focusing on immune checkpoint proteins have yielded significant progress in the treatment of advanced non-small cell lung cancer (NSCLC) in the past few years [1, 2]
In our attempt to explore the characteristic transcriptomic profile of bronchoalveolar lavage (BAL) cells from tumor-bearing lung segments, we first analyzed the differentially expressed genes (DEGs) of BAL cells between the advanced NSCLC patients and the normal controls (NC) in the discovery group, and a total 129 DEGs were identified (Figure 2A)
This study showed that BAL cells of tumor-bearing lung segments displayed a characteristic transcriptomic pattern as a result of the milieu effect of the tumors
Summary
Novel immunotherapies focusing on immune checkpoint proteins have yielded significant progress in the treatment of advanced non-small cell lung cancer (NSCLC) in the past few years [1, 2]. Ample evidences from both murine model and human tumor tissues have revealed that a dual pattern of inflammation around tumors can be recognized conceptually [9] This distinctive presentation in the two ends showing either abundant or sparse immune cells infiltration, appears to play a pivotal role in the prognosis of NSCLCs and as a means of understanding the complex interactions between tumors and their neighboring environments [10]. The immune cells in the local environments surrounding non-small cell lung cancer (NSCLC) implicate the balance of pro- and antitumor immunity; their transcriptomic profiles remain poorly understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
