Immunohistochemical and Image Analysis-Based Study Shows That Several Immune Checkpoints are Co-expressed in Non–Small Cell Lung Carcinoma Tumors

Parra, Edwin R.; Villalobos, Pamela; Zhang, Jiexin; Behrens, Carmen; Mino, Barbara; Swisher, Stephen G.; Sepesi, Boris; Weissferdt, A.; Kalhor, Neda; Heymach, John V.; Moran, César A.; Lee, John; Rodriguez‐Canales, Jaime; Gibbons, Don L.; Wistuba, Ignacio I.

doi:10.1016/j.jtho.2018.03.002

Cited by 59 publications

(63 citation statements)

References 42 publications

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“…All these results revealed that patients with Phenotype A might potentially be more sensitive to immunotherapy than patients with Phenotype B and that the novel classifier could be effective, but these results should be further addressed in large prospective clinical trials. Moreover, although TMAs have been widely used in previous studies and implemented for large population studies because of their convenience, they might reflect only parts of cell components and immune activation in the TME 34‐37 . Hence, TMAs have a limited ability to capture the heterogeneity in infiltrating immune cells, the immune response and tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a stromal immune phenotype classifier for predicting immune activity and prognosis in triple‐negative breast cancer

Zheng

Zou

Xie

et al. 2020

Intl Journal of Cancer

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Our study aims to construct a prognosis-related immune phenotype classifier for predicting clinical prognosis and immune activity in triple-negative breast cancer (TNBC). A total of 237 patients with TNBC from Sun Yat-sen University Cancer Center (SYSUCC) and 533 patients with TNBC from public datasets were included in our study. A stromal immune quantified index was generated with a LASSO Cox regression model based on five prognosis-related immune cells evaluated by CIBERSORT or IHC and was used to determine immune phenotypes. Immune features were evaluated in the samples before chemotherapy. A total of 119 patients in the SYSUCC training cohort were classified into immune Phenotypes A and B according to the density of stromal CD4+ T cells, γδ T cells, monocytes, M1 macrophages and M2 macrophages. Phenotype A predicted better survival than Phenotype B, and the classification was further validated in the testing cohort of 118 patients and the validation cohort of 533 patients. In the combined cohort, significant differences were found in Phenotype A compared to Phenotype B for the 5-year overall survival (83.5% vs 65.8%, respectively, P < .01) and the 5-year disease-free survival (87.3% vs 76.0%, respectively, P < .01). In Phenotype A, immune-related pathways were significantly enriched, and a higher level of immune checkpoint molecules, including PD-L1, PD-1 and CTLA-4, could be observed. The immune phenotype classification was an independent prognostic indicator for TNBC and might serve as a potential predictor for immune activity within the tumor microenvironment. K E Y W O R D Sclassifier, immune phenotype, prognosis, stromal immune score, triple-negative breast cancer

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Section: Discussionmentioning

confidence: 99%

Development and validation of a stromal immune phenotype classifier for predicting immune activity and prognosis in triple‐negative breast cancer

Zheng

Zou

Xie

et al. 2020

Intl Journal of Cancer

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“…Notably, clinical efficacy has been well documented in patients with different types of cancer treated with anti‐PD‐1 mAb . PD‐1 expression has been detected in different immune cells, including T, B and myeloid cells while limited information exists on the PD‐1 expression on ILC . A recent study reported the presence of PD‐1 + NK cells in the ascitic fluid of ovarian carcinoma, while, the expression of PD‐1 on other ILC subsets, particularly in tumors, has not been reported .…”

Section: Discussionmentioning

confidence: 99%

“…The programmed death‐1 (PD‐1, CD279) receptor is an important checkpoint involved in peripheral immune tolerance, thanks to its ability to inhibit cytolytic effector T cells, to prevent their attack towards normal tissues and to control the overreaction of the immune system and consequent tissue damages . PD‐1 pathway may sharply inhibit the function of effector cells, potentially able to kill tumor cells, including cytolytic T lymphocytes and NK cells, through the interaction with their corresponding ligands (PD‐L1/2) expressed on tumor cells . Recent studies, in patients with ovarian carcinoma, have shown that NK cells may express PD‐1.…”

Section: Introductionmentioning

confidence: 99%

Presence of innate lymphoid cells in pleural effusions of primary and metastatic tumors: Functional analysis and expression of PD‐1 receptor

Tumino

Martini

Munari

et al. 2019

Intl Journal of Cancer

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The tumor microenvironment (TM) contains a wide variety of cell types and soluble factors capable of suppressing immune responses. While the presence of NK cells in pleural effusions (PE) has been documented, no information exists on the presence of other innate lymphoid cell (ILC) subsets and on the expression of programmed cell death‐1 (PD‐1) in NK and ILC. The presence of ILC was assessed in PE of 54 patients (n = 33 with mesothelioma, n = 15 with adenocarcinoma and n = 6 with inflammatory pleural diseases) by cell staining with suitable antibody combinations and cytofluorimetric analysis. The cytokine production of ILC isolated from both PE and autologous peripheral blood was analyzed upon cell stimulation and intracytoplasmic staining. We show that, in addition to NK cells, also ILC1, ILC2 and ILC3 are present in malignant PE and that the prevalent subset is ILC3. PE‐ILC subsets produced their typical sets of cytokines upon activation. In addition, we analyzed the PD‐1 expression on NK/ILC by multiparametric flow‐cytometric analysis, while the expression of PD‐1 ligand (PD‐L1) was evaluated by immunohistochemical analysis. Both NK cells and ILC3 expressed functional PD‐1, moreover, both tumor samples and malignant PE‐derived tumor cell lines were PD‐L1+ suggesting that the interaction between PD‐1+ILC and PD‐L1+tumor cells may hamper antitumor immune responses mediated by NK and ILC.

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“…Clinicopathological studies have indicated the positive correlation between KRAS mutations and PD-L1 expression in NSCLC [ 80 , 85 , 87 , 88 , 96 , 98 , 99 , 100 ]. Scheel et al reported that KRAS -mutated NSCLC tumors exhibited a higher positivity of PD-L1 expression [ 98 ].…”

Section: Pd-l1 Expression and Immunologic Features In Oncogene-drimentioning

confidence: 99%

“…Zdanov et al suggested that mutant KRAS induced the secretion of IL-10 and transforming growth factor-β1 (TGF-β1) and contributed to the induction of regulatory T cells [ 106 ]. The most recent clinicopathological study demonstrated that KRAS -mutant LUAD specimens exhibited higher expression of PD-L1 in malignant cells and of B7-H3, T-cell immunoglobulin mucin family member 3 (TIM3), and indoleamine 2, 3-dioxygenase-1 (IDO-1) in stromal tumor-associated inflammatory cells than wild-type [ 100 ].…”

Section: Pd-l1 Expression and Immunologic Features In Oncogene-drimentioning

confidence: 99%

Role of Immunotherapy for Oncogene-Driven Non-Small Cell Lung Cancer

Miura¹,

Sunaga²

2018

Cancers

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The clinical application of immune checkpoint inhibitors (ICIs) has led to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Despite the observation of improved overall survival in NSCLC patients treated with ICIs, their efficacy varies greatly among different immune and molecular profiles in tumors. Particularly, the clinical significance of ICIs for oncogene-driven NSCLC has been controversial. In this review, we provide recent clinical and preclinical data focused on the relationship between oncogenic drivers and immunological characteristics and discuss the future direction of immunotherapy in NSCLC patients harboring such genetic alterations

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Immunohistochemical and Image Analysis-Based Study Shows That Several Immune Checkpoints are Co-expressed in Non–Small Cell Lung Carcinoma Tumors

Abstract: We found frequent immunohistochemical co-expression of immune checkpoints in surgically resected NCLC tumors and correlated with tumor histology, smoking history, tumor size, and the density of inflammatory cells and tumor mutational status.

Cited by 59 publications

References 42 publications

Development and validation of a stromal immune phenotype classifier for predicting immune activity and prognosis in triple‐negative breast cancer

Development and validation of a stromal immune phenotype classifier for predicting immune activity and prognosis in triple‐negative breast cancer

Presence of innate lymphoid cells in pleural effusions of primary and metastatic tumors: Functional analysis and expression of PD‐1 receptor

Role of Immunotherapy for Oncogene-Driven Non-Small Cell Lung Cancer

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