Intratumoral CD56bright natural killer cells are associated with improved survival in bladder cancer
| Autor: | Andrew J. Braun, Qianqian Liu, Robert S. Svatek, Tyler J. Curiel, Jianhua Ruan, Marcela Aguilera, Marlo M. Nicolas, Kerri kendrick, Niannian Ji, Neelam Mukherjee, Dharam Kaushik, Maureen O. Montgomery, Vincent Hurez |
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| Rok vydání: | 2018 |
| Předmět: |
Oncology
medicine.medical_specialty Bladder cancer business.industry Tumor-infiltrating lymphocytes medicine.medical_treatment In vitro cytotoxicity Cancer therapy Improved survival medicine.disease 3. Good health 03 medical and health sciences 0302 clinical medicine Cytokine Bladder Tissue 030220 oncology & carcinogenesis Internal medicine T cell subset Medicine business 030215 immunology |
| Zdroj: | Oncotarget. 9:36492-36502 |
| ISSN: | 1949-2553 |
| Popis: | // Neelam Mukherjee 1 , Niannian Ji 1 , Vincent Hurez 2 , Tyler J. Curiel 2 , Maureen O. Montgomery 1 , Andrew J. Braun 1 , Marlo Nicolas 3 , Marcela Aguilera 5 , Dharam Kaushik 1 , Qianqian Liu 4 , Jianhua Ruan 5 , Kerri A. Kendrick 1 and Robert S. Svatek 1 1 Department of Urology, University of Texas Health San Antonio (UTHSA), San Antonio, United States 2 Department of Medicine, University of Texas Health San Antonio (UTHSA), San Antonio, United States 3 Department of Pathology, University of Texas Health San Antonio (UTHSA), San Antonio, United States 4 Department of Epidemiology & Biostatistics, University of Texas Health San Antonio (UTHSA), San Antonio, United States 5 Department of Computer Science, University of Texas San Antonio (UTSA), San Antonio, United States Correspondence to: Robert S. Svatek email: svatek@uthscsa.edu Keywords: bladder cancer; NK cells; tumor-infiltrating lymphocytes; CD56; survival Received: September 26, 2018 Accepted: November 01, 2018 Published: November 23, 2018 ABSTRACT Background: Natural killer (NK) cells are effective at killing tumors in a non-MHC restricted manner and are emerging targets for cancer therapy but their importance in bladder cancer (BC) is poorly defined. NK cells are commonly subdivided into populations based on relative surface expression of CD56. Two major subsets are CD56 bright and CD56 dim NK cells. Methods: The prevalence of intratumoral lymphocytes was examined via flow cytometric analysis of bladder tissue from a local cohort of patients with non-invasive and invasive BC (n=28). The association of NK cell subsets with cancer-specific survival (CSS) and overall survival (OS) was examined in 50 patients with BC using Cox regression. Fluorescence-activated cell sorting (FACS) of intratumoral lymphocytes isolated CD56 NK cell subsets were used for examination of function, including cytokine production and in vitro cytotoxicity. Results: NK cells predominated among bladder intratumoral lymphocytes. Intratumoral CD56 bright NK cells showed increased cytokine production and cytotoxicity compared to their CD56 dim counterparts and were associated with improved CSS and OS independent of pathologic tumor stage. On the other hand, CD56 dim NK cells were not associated with improved outcomes but were associated with higher pathologic stage. Conclusions: NK cells are frequent among intratumoral lymphocytes in BC. Bladder intratumoral CD56 bright NK cells are functional and prognostically relevant whereas CD56 dim NK cells are dysfunctional and prevalent in higher stage tumors. Thus, CD56 bright NK cells are promising targets in BC. |
| Databáze: | OpenAIRE |
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