Lung cancer is associated with decreased expression of perforin, granzyme B and interferon (IFN)-γ by infiltrating lung tissue T cells, natural killer (NK) T-like and NK cells

Hodge, Greg; Barnawi, Jameel; Jurisevic, Craig; Moffat, David; Holmes, Mark; Reynolds, Paul N.; Jersmann, Hubertus; Hodge, Sandra

doi:10.1111/cei.12392

Cited by 111 publications

(75 citation statements)

References 16 publications

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“…Also, we found that the number of cells expressing granzyme B was significantly lower than the cells expressing CD8. Interestingly, it has been reported that a decreased proportion of granzyme B + cells in lung tumors was a result of soluble mediators, not identified yet, secreted probably by cancer cells (36). …”

Section: Discussionmentioning

confidence: 99%

Image Analysis–based Assessment of PD-L1 and Tumor-Associated Immune Cells Density Supports Distinct Intratumoral Microenvironment Groups in Non–small Cell Lung Carcinoma Patients

Parra

Behrens

Rodriguez‐Canales

et al. 2016

Clinical Cancer Research

139

110

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Purpose We investigated the correlation between immunohistochemical PD-L1 expression and tumor-associated immune cells (TAICs) density in non–small cell lung carcinoma (NSCLC) and correlated them with clinicopathologic variables. Experimental Design Tumor tissue specimens from 254 stage I–III NSCLCs [146 adenocarcinomas; 108 squamous cell carcinomas (SCCs)] were examined. PD-L1 expression in malignant cells and macrophages and the density of TAICs expressing CD3, CD4, CD8, CD57, granzyme B, CD45RO, PD-1, FOXP3, and CD68 were evaluated using immunohistochemistry and image analysis. Results Malignant cells PD-L1 H-score > 5 was detected in 23% of adenocarcinomas and 31% of SCCs, and no significant differences were detected comparing both histologies; the median H-score in macrophages was significantly higher in SCC than in adenocarcinoma (P < 0.001). In adenocarcinoma, high malignant cells PD-L1 expression and high TAIC density correlated with solid histology, smoking history, and airflow limitation. Multivariate analysis demonstrated that high CD57-positive cell density correlated with better recurrence-free survival (RFS; P = 0.0236; HR, 0.457) and overall survival (OS; P = 0.0261; HR, 0.481) rates for SCC. High CD68-positive cell density in intratumoral compartment correlated with better RFS (P = 0.0436; HR, 0.553) for adenocarcinoma. The combination of low CD4/CD8/C68-positive cell density and PD-L1 H-score >5 in malignant cells identified small subset of adenocarcinomas with worse outcomes (RFS: P = 0.036; HR, 4.299; OS: P = 0.00034; HR, 5.632). Conclusions We detected different PD-L1 expression and TAIC density patterns in NSCLC. Distinct groups of tumor microenvironment correlated with NSCLC clinicopathologic features, including outcome.

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Section: Discussionmentioning

confidence: 99%

Image Analysis–based Assessment of PD-L1 and Tumor-Associated Immune Cells Density Supports Distinct Intratumoral Microenvironment Groups in Non–small Cell Lung Carcinoma Patients

Parra

Behrens

Rodriguez‐Canales

et al. 2016

Clinical Cancer Research

139

110

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“…Intratumoral NK cells exhibited defects in deegranulation and IFN-γ production. Another study noted release of soluble factors by NSCLC cells that inhibited granzyme B, perforin and IFNγ expression in intratumoral NK cells [120]. These data suggest local impairment of NK cells by the NSCLC tumor microenvironment.…”

Section: Natural Killer Cellsmentioning

confidence: 89%

Cellular and molecular immunology of lung cancer: therapeutic implications

Nguyen

Berim

Agrawal

2014

Expert Review of Clinical Immunology

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Though incidence is declining, the prognosis of lung cancer remains poor. This is likely due to lack of early detection and only recent developments in selective cancer therapies. Key immune cells involved in the pathogenesis of lung cancer include CD4+ T-lymphocytes, macrophages, dendritic cells, and natural killer cells. The growing understanding of these cells indicates a highly complex and intertwined network of their involvement in each stage of lung cancer. Immune cell types and numbers affect prognosis and could offer an opportunity for clinical therapeutic applications. However, an incomplete understanding of immune cell involvement and the underlying processes in lung cancer still remain. More investigation focusing on the role of the immune cells will further the understanding of lung carcinogenesis and develop novel therapeutic approaches for the treatment and management of patients with more specialized and selective lung cancer.

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“…Many reports have indicated that the dysfunction of NK cell and NKT cell is closely related to the occurrence and development of lung cancer (Hasegawa et al, 2014;Hodge et al, 2014), but the underlying molecular mechanisms involved in this process remain poorly understood. Tim-3, was originally identified for Th1-specific markers.…”

Section: Discussionmentioning

confidence: 99%

Tim-3 Expression by Peripheral Natural Killer Cells and Natural Killer T Cells Increases in Patients with Lung Cancer - Reduction after Surgical Resection

Chen²,

He³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Lung cancer is associated with decreased expression of perforin, granzyme B and interferon (IFN)-γ by infiltrating lung tissue T cells, natural killer (NK) T-like and NK cells

Cited by 111 publications

References 16 publications

Image Analysis–based Assessment of PD-L1 and Tumor-Associated Immune Cells Density Supports Distinct Intratumoral Microenvironment Groups in Non–small Cell Lung Carcinoma Patients

Image Analysis–based Assessment of PD-L1 and Tumor-Associated Immune Cells Density Supports Distinct Intratumoral Microenvironment Groups in Non–small Cell Lung Carcinoma Patients

Cellular and molecular immunology of lung cancer: therapeutic implications

Tim-3 Expression by Peripheral Natural Killer Cells and Natural Killer T Cells Increases in Patients with Lung Cancer - Reduction after Surgical Resection

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