NK and T cells with a cytotoxic/migratory phenotype accumulate in peritumoral tissue of patients with clear cell renal carcinoma
Language English Country United States Media print-electronic
Document type Journal Article, Observational Study, Research Support, Non-U.S. Gov't
PubMed
31030972
DOI
10.1016/j.urolonc.2019.03.014
PII: S1078-1439(19)30110-3
Knihovny.cz E-resources
- Keywords
- FasL, PECAM-1, Renal cell carcinoma, TRAIL, Tumor-infiltrating lymphocytes, peritumoral,
- MeSH
- Platelet Endothelial Cell Adhesion Molecule-1 metabolism MeSH
- Killer Cells, Natural immunology metabolism MeSH
- Cytotoxicity, Immunologic MeSH
- Carcinoma, Renal Cell immunology pathology surgery MeSH
- Kidney cytology immunology pathology surgery MeSH
- Middle Aged MeSH
- Humans MeSH
- Fas Ligand Protein metabolism MeSH
- Kidney Neoplasms immunology pathology surgery MeSH
- Nephrectomy MeSH
- TNF-Related Apoptosis-Inducing Ligand metabolism MeSH
- Flow Cytometry MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Cell Separation MeSH
- T-Lymphocytes immunology metabolism MeSH
- Lymphocytes, Tumor-Infiltrating immunology metabolism MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Platelet Endothelial Cell Adhesion Molecule-1 MeSH
- FASLG protein, human MeSH Browser
- Fas Ligand Protein MeSH
- PECAM1 protein, human MeSH Browser
- TNF-Related Apoptosis-Inducing Ligand MeSH
- TNFSF10 protein, human MeSH Browser
OBJECTIVES: Renal cell carcinoma (RCC) is the most lethal urologic malignancy with increasing incidence worldwide. The conventional treatment strategies for advanced or recurrent RCC are not efficient and show considerable toxicities. Adoptive cell transfer (ACT) has become a promising treatment option for multiple cancers, particularly in combination with other therapeutic approaches. ACT often utilizes extensively in vitro expanded tumor-infiltrating lymphocytes (TILs). However, TILs are a very heterogeneous mix of cell populations and only those populations that have a cytotoxic and migratory potential are thought to deliver a therapeutic impact in ACT. The identification and localization of these therapeutically potent populations are therefore needed. METHODS AND MATERIALS: A total number of 57 tissue samples from 19 RCC patients who underwent radical nephrectomy was analyzed. The tissue samples were obtained from the tumor, peritumoral tissue, and the adjacent healthy renal tissue. The tissues were sliced, enzymatically dissociated into single cell suspensions and the obtained cells further analyzed by flow cytometry for the expression of markers of lymphocyte cytotoxicity - TRAIL and FasL, and a surrogate marker of lymphocyte migratory activity - PECAM-1. The analyzed data were next correlated with the clinical and histopathological data. RESULTS: Non-clear cell RCC (non-ccRCC) tumors showed a significantly decreased tumor infiltration with TRAIL+FasL+ NK cells but elevated infiltration with FasL+PECAM-1+ T cells as compared with clear cell RCC (ccRCC) tumors. Further analyses revealed that the peritumoral tissue of ccRCC patients is a reservoir of TRAIL+FasL+, TRAIL+PECAM-1+, or FasL+PECAM-1+ NK and T cells. CONCLUSIONS: The cytotoxic/migratory lymphocytes were identified in tumors of ccRCC patients. These lymphocytes became excluded from the tumor and accumulated in the patient's peritumoral tissue.
References provided by Crossref.org
The Role of miR-155 in Antitumor Immunity
The challenges of adoptive cell transfer in the treatment of human renal cell carcinoma
