Characteristics of Malignant Pleural Effusion Resident CD8+ T Cells from a Heterogeneous Collection of Tumors
| Autor: | Seth H. Eisenberg, Tullia C. Bruno, Adam C. Soloff, Sara E. Monaco, Dongyan Liu, Michael T. Lotze, James D. Luketich, Olugbenga T. Okusanya, Udai S. Kammula, Ayana T. Ruffin, Rajeev Dhupar |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male CD8-Positive T-Lymphocytes lcsh:Chemistry chemistry.chemical_compound 0302 clinical medicine Neoplasms Tumor Cells Cultured Malignant pleural effusion Cytotoxic T cell tumor immunosuppression lcsh:QH301-705.5 Spectroscopy Aged 80 and over Cell Differentiation General Medicine Middle Aged Computer Science Applications Gene Expression Regulation Neoplastic medicine.anatomical_structure 030220 oncology & carcinogenesis Female Receptors CCR7 T cell Biology Article Catalysis Inorganic Chemistry Interleukin-7 Receptor alpha Subunit 03 medical and health sciences Interferon-gamma Immune system metastatic cancer Lactate dehydrogenase medicine Humans malignant pleural effusion Lactic Acid Physical and Theoretical Chemistry Interleukin-7 receptor Molecular Biology Aged Neoplasm Staging L-Lactate Dehydrogenase Myeloid-Derived Suppressor Cells Organic Chemistry medicine.disease T cell response Coculture Techniques Pleural Effusion Malignant 030104 developmental biology chemistry lcsh:Biology (General) lcsh:QD1-999 Cancer research Myeloid-derived Suppressor Cell Leukocyte Common Antigens CD8 |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 17 International Journal of Molecular Sciences, Vol 21, Iss 6178, p 6178 (2020) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21176178 |
| Popis: | While T cell-based cancer immunotherapies have shown great promise, there remains a need to understand how individual metastatic tumor environments impart local T cell dysfunction. At advanced stages, cancers that metastasize to the pleural space can result in a malignant pleural effusion (MPE) that harbors abundant tumor and immune cells, often exceeding 108 leukocytes per liter. Unlike other metastatic sites, MPEs are readily and repeatedly accessible via indwelling catheters, providing an opportunity to study the interface between tumor dynamics and immunity. In the current study, we examined CD8+ T cells within MPEs collected from patients with heterogeneous primary tumors and at various stages in treatment to determine (1) if these cells possess anti-tumor activity following removal from the MPE, (2) factors in the MPE that may contribute to their dysfunction, and (3) the phenotypic changes in T cell populations that occur following ex vivo expansion. Co-cultures of CD8+ T cells with autologous CD45― tumor containing cells demonstrated cytotoxicity (p = 0.030) and IFN&gamma production (p = 0.003) that inversely correlated with percent of myeloid derived suppressor cells, lactate, and lactate dehydrogenase (LDH) within the MPE. Ex vivo expansion of CD8+ T cells resulted in progressive differentiation marked by distinct populations expressing decreased CD45RA, CCR7, CD127, and increased inhibitory receptors. These findings suggest that MPEs may be a source of tumor-reactive T cells and that the cellular and acellular components suppress optimal function. |
| Databáze: | OpenAIRE |
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