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Quantitative Assessment of CD200 and CD200R Expression in Lung Cancer.

ABSTRACT: CD200/CD200R is an immune checkpoint with broad expression patterns and a potential target for immune therapy. In this study, we assess both CD200 and CD200R expression in solid tumors, with a focus on lung cancer, and evaluate their association with clinicopathologic characteristics, mutation status, outcome, and programmed death-ligand 1 (PD-L1) expression. We used multiplexed quantitative immunofluorescence (QIF) to measure the expression of CD200 and CD200R in a total of 455 patients from three lung cancer cohorts. Using carefully validated antibodies, we performed target measurement with tyramide-based QIF panels and analyzed the data using the PM2000 microscope and AQUA software. CD200 tumor positivity was found in 29.7% of non-small cell lung cancer (NSCLC) patients and 33.3% of lung large cell neuroendocrine carcinoma (LCNEC) patients. CD200 demonstrated notable intratumoral heterogeneity. CD200R was expressed in immune cells in 25% of NSCLC and 41.3% of LCNEC patients. While CD200R is predominantly expressed in immune cells, rare tumor cell staining was seen in a highly heterogeneous pattern. CD200R expression in the stromal compartment was significantly higher in patients with squamous differentiation (p < 0.0001). Neither CD200 nor CD200R were associated with other clinicopathologic characteristics or mutation status. Both biomarkers were not prognostic for disease-free or overall survival in NSCLC. CD200 showed moderate correlation with PD-L1. CD200/CD200R pathway is frequently expressed in lung cancer patients. Differential expression patterns of CD200 and CD200R with PD-L1 suggest a potential role for targeting this pathway alone in patients with NSCLC.

SUBMITTER: Vathiotis IA

PROVIDER: S-EPMC7957629 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Rabbit CD200R binds host CD200 but not CD200-like proteins from poxviruses.

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| S-EPMC1955461 | biostudies-literature

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Project description:Non-small cell lung carcinoma (NSCLC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related deaths. Immunotherapy with immune checkpoint inhibitors shows beneficial responses, but only in a proportion of patients. To improve immunotherapy in NSCLC, we need to map the immune checkpoints that contribute immunosuppression in NSCLC-associated immune cells and to identify novel pathways that regulate immunosuppression. Here, we investigated the gene expression profiles of intra-tumoral immune cells isolated from NSCLC patients and compared them to the expression profiles of their counterparts in adjacent healthy tissue. Transcriptome analysis was performed on macrophages, CD4+ and CD8+ T cells. The data was subjected to Gene Ontology (GO) term enrichment and weighted correlation network analysis in order to identify mediators of immunosuppression in the tumor microenvironment in NSCLC. Immune cells from NSCLC revealed a consistent differential expression of genes involved in interactions between myeloid cells and lymphocytes. We further identified several immunosuppressive molecules and pathways that may be activated in tumor-associated macrophages in NSCLC. Importantly, we report novel data on immune cell expression of the newly described CD200/CD200R1 pathway, and the leukocyte immunoglobulin-like receptors (LILRs), which may represent novel innate immune checkpoints, dampening the anti-tumor T cell immune response in NSCLC. Our study substantiates the importance of tumor-associated macrophages as a mediator of immunosuppression and a promising target for immunotherapy.

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Project description:Background CD200-CD200R plays a critical role in regulating the human tumor microenvironment, but its role in cervical cancer remains unclear. Methods A total of 62 paraffin blocks of tumor tissues were collected from cervical cancer patients. Expression of CD200 and cathepsin K (CTSK) in cancer tissues and para-cancerous tissues was analyzed by immunohistochemistry. Stably transfected CD200 cells were established in HeLa and SiHa cells. Human THP-1 monocytes were induced to differentiate into M2 macrophages. HeLa and SiHa cells were cultured in conditioned medium from M2 macrophages to observe the effects of CD200-CD200R on invasion, CTSK, p65NF-κB, and cisplatin or paclitaxel sensitivity in cervical cancer cells. HeLa cells were injected to induce xenograft tumors in mice, and a CTSK inhibitor, MK-0822, was used to confirm the regulation of CTSK and paclitaxel sensitivity by CD200-CD200R in vivo. Results A significant decrease in CD200 and CTSK expression was found in tumor cancer tissues compared with para-cancerous tissues. Only CD200 overexpression did not affect cervical cell invasion, but CD200-CD200R could enhance the cell invasion and resistance to cisplatin or paclitaxel. Meanwhile, expression of CTSK and p-p65NF-κB in cancer cells stably transfected with CD200 was obviously increased after culture in conditioned medium from M2 macrophages compared with transfection with the plasmid control. In vivo, CTSK inhibition significantly suppressed the effects of CD200-CD200R overexpression on the response to paclitaxel by suppressing the CTSK-mediated NF-κB pathway. Conclusions CD200-CD200R regulates CTSK-mediated NF-κB pathway to affect cisplatin or paclitaxel sensitivity in cervical cancer, which provides a possible immunotherapeutic target and combination strategy for advanced cervical cancer.

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