Cell by cell immuno- and cancer marker profiling of non-small cell lung cancer tissue: Checkpoint marker expression on CD103+, CD4+ T-cells predicts circulating tumor cells
| العنوان: | Cell by cell immuno- and cancer marker profiling of non-small cell lung cancer tissue: Checkpoint marker expression on CD103+, CD4+ T-cells predicts circulating tumor cells |
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| المؤلفون: | Priya Gogoi, Maria Jaimes, Vishal P. Sharma, Keith Shults, Will Chow, Bruce K. Patterson, Santosh Putta, Huimin Gu, Kalyan Handique, Xiaoyang Wang |
| المصدر: | Translational Oncology Translational Oncology, Vol 14, Iss 1, Pp 100953-(2021) |
| بيانات النشر: | Neoplasia Press, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Original article, CCR5, CC chemokine receptor 5, medicine.medical_treatment, TIM-3, mucin domain-3-containing molecule-3, TIL, tumor infiltrating lymphocyte, lcsh:RC254-282, High parameter flow cytometry, Targeted therapy, Cancer marker, 03 medical and health sciences, 0302 clinical medicine, Circulating tumor cell, Non-small cell lung cancer, medicine, Tumor infiltrating lymphocyte, neoplasms, LAG-3, lymphocyte-activation gene-3, biology, Tumor-infiltrating lymphocytes, ALK, anaplastic lymphoma kinase, CD44, TME, tumor microenvironment, Immunotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Aneuploidy, Immune checkpoint, respiratory tract diseases, EGFR, epidermal growth factor receptor, PD-L1, programmed death-ligand 1, 030104 developmental biology, Oncology, Tumor microenvironment, CTLA-4, 030220 oncology & carcinogenesis, Cancer cell, biology.protein, Cancer research, PD-1, programmed death-1, CTLA-4, cytotoxic T-lymphocyte antigen-4, CCR5, LAG3 |
| الوصف: | Highlights • CTCs in NSCLC correlate with the presence of Treg cells expressing checkpoint markers in the tumor microenvironment. • Treg cells in NSCLC express CCR5, a new class of drug targets in inhibiting tumor growth and metastasis. • NSCLC tumors have a signature that is predictive of the presence of CTCs. • Highly multiplexed immune profiling reveals different patterns of expression in diploid compared to aneuploidy tumor cells from the same tumor. • Highly sensitive CTC enumeration methodology. Non-small cell lung cancer (NSCLC) has a poor prognosis. Targeted therapy and immunotherapy in recent years has significantly improved NSCLC patient outcome. In this study, we employed cell-by-cell immune and cancer marker profiling of the primary tumor cells to investigate possible signatures that might predict the presence or absence of circulating tumor cells (CTCs). We performed a comprehensive study on 10 NSCLC patient tissue samples with paired blood samples. The solid tissue biopsy samples were dissociated into single cells by non-enzymatic tissue homogenization and stained with a total 25 immune, cancer markers and DNA content dye and analyzed with high-parameter flow cytometry. CTCs were isolated and analyzed from the paired peripheral blood. We investigated a total of 74 biomarkers for their correlation with CTC number. Strong correlations were observed between CTC number and the frequency of immune checkpoint marker expressing lymphocytes (CTLA-4, LAG3, TIM3, PD-1), within the CD103+CD4+ T lymphocyte subset. CTC number is also correlated with the frequency of PD-L1 expressing cancer cells and cancer cell DNA content. In contrast, CTC number inversely correlated to the frequency of CD44+E-cadherin− cancer cells. Unsupervised clustering analysis based on the biomarker analysis separated the CTC negative patients from the CTC positive patients. Profiling multiple immune and cancer markers on cancer samples with multi-parametric flow cytometry allowed us to obtain protein expression information at the single cell level. Clustering analysis of the proteomic data revealed a signature driven by checkpoint marker expression on CD103+CD4+ T cells that could potentially be predictive of CTCs and targets of therapy. |
| اللغة: | English |
| تدمد: | 1936-5233 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecab16bcda00a3c50791646d2116fe51Test http://europepmc.org/articles/PMC7683336Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ecab16bcda00a3c50791646d2116fe51 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19365233 |
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