Chronic Obstructive Pulmonary Disease Alters Immune Cell Composition and Immune Checkpoint Inhibitor Efficacy in Non–Small Cell Lung Cancer

Mark, Nicholas M.; Kargl, Julia; Busch, Stephanie; Yang, Guangning; Metz, Heather; Zhang, Huajia; Hubbard, Jesse J.; Pipavath, Sudhakar; Madtes, David K.; Houghton, A. McGarry

doi:10.1164/rccm.201704-0795oc

Cited by 93 publications

(155 citation statements)

References 48 publications

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“…T‐helper cell type 1 (Th1) differentiation of lymphocytes increases in the tumor microenvironment of patients with NSCLC and COPD, which is in line with COPD pathogenesis. However, analyses of fresh tumor samples showed greater exhaustion of CD8+ tumor‐infiltrating lymphocytes (TILs) in patients with COPD . Exhausted T cells show a dysfunctional tumor‐specific immune response, with reduced cytokine production and decreased survival with increased expression of inhibitory receptors .…”

Section: Discussionmentioning

confidence: 74%

“…Finally, we lacked data regarding the immune profile or tumor mutational burden (TMB) of the patients who received an ICI. Unfortunately, this limitation is shared by previous studies, due to the scarcity of fresh lung tissue from patients who received an ICI . The potential mechanism underlying increased TIL in patients with COPD could be related to higher TMB of NSCLC, developing in the context of COPD, given the better response to ICI in patients with a higher TMB (particularly in those with smoking‐associated lung cancer) .…”

Section: Discussionmentioning

confidence: 98%

“…Recently, extensive immunological studies suggest a higher sensitivity to ICIs in NSCLC patients with COPD compared to those without COPD. The presence of COPD has been associated with longer progression‐free survival (PFS) in patients with NSCLC treated with ICIs, which contrasts with previous reports . However, these studies investigated this association using physician‐diagnosed COPD or in less than 50 patients with spirometry‐defined COPD .…”

Section: Introductionmentioning

confidence: 88%

“…However, these studies investigated this association using physician‐diagnosed COPD or in less than 50 patients with spirometry‐defined COPD . In addition, patients who received nivolumab were mainly included in these previous studies . Therefore, we aimed to investigate the impact of spirometry‐defined COPD on the treatment response to ICIs, in a larger number of NSCLC patients treated with pembrolizumab.…”

Section: Introductionmentioning

confidence: 99%

“…The presence of COPD has been associated with longer progression-free survival (PFS) in patients with NSCLC treated with ICIs, which contrasts with previous reports. 10,11 However, these studies investigated this association using physician-diagnosed COPD 10 or in less than 50 patients with spirometry-defined COPD. 11 In addition, patients who received nivolumab were mainly included in these previous studies.…”

Section: Introductionmentioning

confidence: 99%

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Improved treatment outcome of pembrolizumab in patients with nonsmall cell lung cancer and chronic obstructive pulmonary disease

Shin

Park

et al. 2019

Intl Journal of Cancer

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Emerging immune profiling data suggest a higher sensitivity to immune checkpoint inhibitors (ICIs) in nonsmall cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), compared to those without COPD. This study aimed to investigate the clinical impact of COPD on the treatment response to ICIs in a large number of patients with NSCLC. In total, 133 patients with spirometry test results were retrospectively identified among those who received palliative pembrolizumab for NSCLC. COPD was defined as pre‐bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.7. Overall survival (OS), progression‐free survival (PFS), and objective response rate were analyzed according to the presence of COPD. Spirometry‐based COPD was present in 59 (44%) patients. Patients with COPD had better OS (hazard ratio [HR] for death, 0.45; 95% confidence interval [CI], 0.26–0.78) and PFS (HR for disease progression or death, 0.50; 95% CI, 0.31–0.79) than those without COPD. These associations persisted after adjusting for potential confounders including smoking history. The response rate was also higher in patients with COPD than in those without COPD (38.2% vs. 20.5%, p = 0.028). Spirometry‐defined COPD was associated with a significantly longer OS and PFS in patients with NSCLC treated with palliative pembrolizumab. Identifying coexisting COPD could predict favorable treatment outcomes in patients with NSCLC treated with pembrolizumab.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Improved treatment outcome of pembrolizumab in patients with nonsmall cell lung cancer and chronic obstructive pulmonary disease

Shin

Park

et al. 2019

Intl Journal of Cancer

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MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC

Yin,

Zeng,

Abuduwayiti

et al. 2024

Cancer Medicine

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BackgroundPatients with non‐small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal‐associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD‐associated NSCLC and their involvement in the immune response.MethodsFlow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti‐programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5‐OP‐RU using a mouse subcutaneous tumor model.ResultsTumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8+ MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8+ MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon γ (IFNγ), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5‐OP‐RU enhanced the antitumor effects of anti‐PD1.ConclusionsIn patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8+ MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8+ MAIT cells.

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Neoantigens in Chronic Obstructive Pulmonary Disease and Lung Cancer: A Point of View

Zeneyedpour

Dekker

Hoff

et al. 2019

Proteomics Clinical Apps

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The goal of this manuscript is to explore the role of clinical proteomics for detecting mutations in chronic obstructive pulmonary disease (COPD) and lung cancer by mass spectrometry‐based technology. COPD and lung cancer caused by smoke inhalation are most likely linked by challenging the immune system via partly shared pathways. Genome‐wide association studies have identified several single nucleotide polymorphisms which predispose an increased susceptibility to COPD and lung cancer. In lung cancer, this leads to coding mutations in the affected tissues, development of neoantigens, and different functionality and abundance of proteins in specific pathways. If a similar reasoning can also be applied in COPD will be discussed. The technology of mass spectrometry has developed into an advanced technology for proteome research detecting mutated peptides or proteins and finding relevant molecular mechanisms that will enable predicting the response to immunotherapy in COPD and lung cancer patients.

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Chronic Obstructive Pulmonary Disease Alters Immune Cell Composition and Immune Checkpoint Inhibitor Efficacy in Non–Small Cell Lung Cancer

Cited by 93 publications

References 48 publications

Improved treatment outcome of pembrolizumab in patients with nonsmall cell lung cancer and chronic obstructive pulmonary disease

Improved treatment outcome of pembrolizumab in patients with nonsmall cell lung cancer and chronic obstructive pulmonary disease

MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC

Neoantigens in Chronic Obstructive Pulmonary Disease and Lung Cancer: A Point of View

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