Non‐small cell lung cancer is characterised by a distinct inflammatory signature in serum compared with chronic obstructive pulmonary disease

Eide, H.; Halvorsen, Ann Rita; Sandhu, Vandana; Fåne, Anne; Berg, Janna; Haakensen, Vilde Drageset; Kure, Elin H.; Brustugun, Odd Terje; Kiserud, Cecilie E.; Kyte, Jon Amund; Helland, Åslaug

doi:10.1038/cti.2016.65

Cited by 29 publications

(24 citation statements)

References 38 publications

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“…Matsumoto et al, showed that higher levels of PDGF-bb were associated with poor prognosis in esophageal cancers, 31 while Eide et al found higher PDGF-bb serum levels in lung cancer compared to COPD patients. 32 In the MicMa cohort higher levels of PDGF were associated with worse prognosis, the same tendency although not significant, was observed in the DCTB cohort. The PDGF family of growth factors play a role in lymphangiogenesis.…”

Section: Discussionmentioning

confidence: 68%

Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics

et al. 2018

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Cancers elicit an immune response by modifying the microenvironment. The immune system plays a pivotal role in cancer recognition and eradication. While the potential clinical value of infiltrating lymphocytes at the tumor site has been assessed in breast cancer, circulating cytokines – the molecules coordinating and fine-tuning immune response – are still poorly characterized.Using two breast cancer cohorts (MicMa, n = 131, DCTB, n = 28) and the multiplex Luminex platform, we measured the levels of 27 cytokines in the serum of breast cancer patients prior to treatment. We investigated the cytokine levels in relation to clinicopathological characteristics and in perspective of the tumor infiltrating immune cells predicted from the bulk mRNA expression data.Unsupervised clustering analysis of the serum cytokine levels in the MicMa cohort identified a cluster of pro-inflammatory, pro-angiogenic, and Th2-related cytokines which was associated with poor prognosis. Notably high levels of platelet derived growth factor BB (PDGF) reflected a more aggressive tumor phenotype and larger tumor size. A significant positive correlation between serum levels of interferon gamma-induced protein 10 (IP10) and its mRNA expression at the tumor site suggested that tumor-IP10-production may outflow to the bloodstream. High IP10 serum levels were associated with a worse prognosis. Finally, we found serum levels of both PDGF and IP10 associated with enrichment scores of specific tumor infiltrating immune cells.Our study suggests that monitoring cytokine circulating levels in breast cancer could be used to characterize breast cancers and the immune composition of their microenvironment through readily available biological material.

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Section: Discussionmentioning

confidence: 68%

Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics

et al. 2018

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“…It has been deeply investigated how various elements of the pathogenesis of COPD contributed to pathogenesis of lung cancer. Recently, the shift from Th1 to Th2 polarization of the immune response [40], the accumulation of IL-17 producing Th17 lymphocytes [41], the simultaneous overproduction of certain cytokines, chemokines and matrix metalloproteinases [42] have been raised as possible elements of carcinogenesis in those who smoke and have suffered from COPD previously. *Cox-regression model also included the type of chemotherapy, which did not influence PFS (not shown).…”

Section: Discussionmentioning

confidence: 99%

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

Szentkereszty

Komlósi

Szűcs

et al. 2019

Pathol. Oncol. Res.

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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.

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“…Clinical trials evaluating immune checkpoint inhibitors (ICI), such as antibodies to anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1), have demonstrated that blocking such inhibitory receptors and ligands provides benefit to patients with cancers such as non-small cell lung cancer (NSCLC), urothelial cancer, renal cell carcinoma, melanoma, and ovarian cancer (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Furthermore, patients in whom the immune checkpoint pro-tein PD-L1 is overexpressed on tumor or immune cells (12)(13)(14)(15)(16) show even greater clinical benefit from these therapies.…”

Section: Introductionmentioning

confidence: 99%

Interferon Gamma Messenger RNA Signature in Tumor Biopsies Predicts Outcomes in Patients with Non–Small Cell Lung Carcinoma or Urothelial Cancer Treated with Durvalumab

Higgs¹,

Morehouse²,

Streicher³

et al. 2018

Clinical Cancer Research

174

139

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To identify a predictive biomarker for durvalumab, an anti-programmed death ligand 1 (PD-L1) mAb. RNA sequencing of 97 advanced-stage non-small cell lung carcinoma (NSCLC) biopsies from a nonrandomized phase Ib/II clinical trial (1108/NCT01693562) were profiled to identify a predictive signature; 62 locally advanced or metastatic urothelial cancer tumors from the same study were profiled to confirm predictive utility of the signature. Thirty NSCLC patients provided pre- and posttreatment tumors for messenger RNA (mRNA) analysis. NSCLC with ≥25% tumor cells and urothelial cancer with ≥25% tumor or immune cells stained for PD-L1 at any intensity were scored PD-L1 positive (PD-L1). Kaplan-Meier and Cox proportional hazards analyses were used to adjust for gender, age, prior therapies, histology, ECOG status, liver metastasis, and smoking. Tumor mutation burden (TMB) was calculated using data from The Cancer Genome Atlas (TCGA). In the NSCLC discovery set, a four-gene IFNγ-positive (IFNγ) signature comprising , and was associated with higher overall response rates, longer median progression-free survival, and overall survival compared with signature-low patients. IFNγ-signature NSCLC patients had improved survival regardless of IHC PD-L1 status. These associations were replicated in a urothelial cancer cohort. The IFNγ signature was induced 2-fold ( = 0.003) by durvalumab after 8 weeks of therapy in patients with NSCLC, and baseline signature was associated with TMB but not survival in TCGA data. The IFNγ mRNA signature may assist in identifying patients with improved outcomes with durvalumab, independent of PD-L1 assessed by IHC. .

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Non‐small cell lung cancer is characterised by a distinct inflammatory signature in serum compared with chronic obstructive pulmonary disease

Cited by 29 publications

References 38 publications

Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics

Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics

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

Interferon Gamma Messenger RNA Signature in Tumor Biopsies Predicts Outcomes in Patients with Non–Small Cell Lung Carcinoma or Urothelial Cancer Treated with Durvalumab

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