B Cells and Tertiary Lymphoid Structures Influence Survival in Lung Cancer Patients with Resectable Tumors

Abstract

Simple Summary

Nowadays, humans still die of lung cancer (LC), a disease mainly related to cigarette smoking (CS). Smokers also develop chronic bronchitis, namely chronic obstructive pulmonary disease (COPD). Environmental factors and a natural predisposition from the patients’ sides may render them more prone to develop tumors derived from CS. Thus, a great number of patients may suffer from chronic bronchitis and LC simultaneously. Chronic respiratory diseases are also important risks factors for LC. The immune system, among other biological mechanisms, protect our cells from infections and cancer development. Several immune structures and cells may be altered in the tumors of patients with COPD as opposed to lung tumors of patients with no underlying respiratory disease. A total of 133 patients with LC participated in the study: 93 with underlying COPD. Several structures (tertiary lymphoid structures, TLS) and T and B lymphocytes were analyzed in the lung tumor and non-tumor areas (specimens obtained during surgical extirpation of the tumors). We found that in LC patients with COPD, compared to those without it, fewer numbers of TLSs and B cells were detected, and those patients died significantly earlier. These results have implications in the diagnosis and treatment options of lung tumors in patients with underlying respiratory diseases.

Abstract

Immune profile of B and T cells and tertiary lymphoid structures (TLSs) may differ in tumors of lung cancer (LC) patients with/without chronic obstructive pulmonary disease (COPD), and may also influence patient survival. We sought to analyze: (1) TLSs, germinal centers (GCs), B and T cells, and (2) associations of the immune biomarkers with the patients’ 10-year overall survival (OS). TLSs (numbers and area), B [cluster of differentiation (CD) 20], and T (CD3), and GCs cells were identified in both tumor and non-tumor specimens (thoracotomy) from 90 LC-COPD patients and 43 LC-only patients. Ten-year OS was analyzed in the patients. Immune profile in tumors of LC-COPD versus LC: TLS numbers and areas significantly decreased in tumors of LC-COPD compared to LC patients. No significant differences were observed in tumors between LC-COPD and LC patients for B or T cells. Immune profile in tumors versus non-tumor specimens: TLS areas and B cells significantly increased, T cells significantly decreased in tumors of both LC and LC-COPD patients. Survival: in LC-COPD patients: greater area of TLSs and proportion of B cells were associated with longer survival rates. The immune tumor microenvironment differs in patients with underlying COPD and these different phenotypes may eventually impact the response to immunotherapy in patients with LC.