Effect of COPD on Inflammation, Lymphoid Functions and Progression-Free Survival during First-Line Chemotherapy in Advanced Non-small Cell Lung Cancer

Abstract

Chronic obstructive pulmonary disease (COPD) is a common comorbidity of non-small cell lung cancer (NSCLC). COPD is characterized by systemic inflammation and lymphocyte dysfunction, mechanisms that are also known to accelerate progression of advanced (IIIB-IV) stage NSCLC. We aimed to find out whether COPD exerts an influence on tumor induced inflammatory and lymphoid responses and progression-free survival (PFS) after first-line treatment in advanced NSCLC. Patients suffering from NSCLC (n = 95), COPD (n = 54), NSCLC+COPD (n = 80) and healthy controls (n = 60) were included. PFS, neutrophil granulocyte and lymphocyte cell counts were recorded. Serum IFNγ, TNFα, VEGF concentrations were measured by using multiplex cytometric bead-based immunoassay. Prevalence of myeloid-derived suppressor cell populations (MDSC-s), and signs of T cell exhaustion were tested by using flow cytometry. Median PFS increased in the NSCLC+COPD group compared to NSCLC patients without COPD (7.4 vs 4.9 months, p < 0.01). NSCLC+COPD patients had 1.7 times (1.2-2.4) more likely to have longer PFS compared to NSCLC patients without COPD (Cox analysis, p < 0.01). Neutrophil cell counts, CRP, IFNγ and TNFα concentrations were all reduced in NSCLC+COPD (all p < 0.05 vs NSCLC). NSCLC+COPD was also associated with reduced serum IL-10 concentration and increased granzyme-B positive CD8 cell counts compared to NSCLC without COPD. The effects of VEGF and MDSC-s on systemic inflammation appeared to be blunted by COPD in patients suffering from advanced NSCLC. Concomitant COPD moderates tumor-induced inflammation and supports some effector lymphoid functions and thereby may be an independent positive predictive factor of longer PFS after first-line therapy in advanced NSCLC.

<p>Impact of Combined Chronic Obstructive Pulmonary Disease Status and Systemic Inflammation on Outcome of Advanced NSCLC: Multicenter Retrospective Cohort Study</p>

“…From the study by Szentkereszty et al, the levels of IFNγ, TNFα, IL-10, and NLR were significantly different between a COPD and a non-COPD NSCLC group. 36 However, there was no significant difference in the levels of NLR and PLR between COPD and non-COPD groups in our study. This may be due to the considerable proportion of patients with mild COPD in our study population, who did not show evident deterioration of lung function.…”

Identification of predictive factors for early relapse in patients with unresectable stage III non‐small cell lung cancer receiving consolidation durvalumab after concurrent chemoradiation therapy

“…In a retrospective study of NSCLC patients treated with ICIs, differences were not found in histological subtype, PD‐L1 expression, and OS between COPD and non‐COPD patients 31 . Conversely, advanced NSCLC patients with concomitant COPD showed prolonged PFS after platinum‐based chemotherapy compared with NSCLC patients without COPD in other studies 32 . Presence of COPD was also associated with longer PFS in patients treated with ICIs which might be due to the expansion of the Th1 cell population in both lung and tumor microenvironments 33 .…”

Impact of chronic obstructive pulmonary disease on the efficacy and safety of neoadjuvant immune checkpoint inhibitors combined with chemotherapy for resectable non-small cell lung cancer: a retrospective cohort study

“…Biton et al revealed that the presence of COPD can up-regulate the expression of PD-1 and TIM3 on the surface of CD8 + T lymphocytes, resulting in the depletion of infiltrating T lymphocytes in the tumor microenvironment [ 24 ]. Furthermore, COPD also causes changes in the ratio of Treg/Th17 cells, a decrease in granulocyte myeloid-derived suppressor cells, and an increase in PD-1 + tumor-associated macrophages [ 11 , 16 , 25 ]. In addition to the changes in the tumor immune microenvironment, an increased expression of PD-L1 in tumor cells [ 11 , 26 ], promoter methylation of CTLA4 , LAG3 , and PD-L1 , and an abnormal expression of microRNAs [ 27 – 29 ] can affect the efficacy of ICIs in NSCLC patients with COPD.…”