Intratumoral CD56^bright natural killer cells are associated with improved survival in bladder cancer

The cover for issue 92 of Oncotarget features Figure 4, "Intratumoral CD56^bright NK cells are more functional than CD56^dim NK cells and correlate with survival in bladder cancer," by Mukherjee, et al.

Fluorescence-activated cell sorting of intratumoral lymphocytes isolated CD56 NK cell subsets were used for examination of function, including cytokine production and in vitro cytotoxicity. NK cells predominated among bladder intratumoral lymphocytes. Bladder intratumoral CD56^bright NK cells are functional and prognostically relevant whereas CD56^dim NK cells are dysfunctional and prevalent in higher stage tumors.

Dr. Robert S. Svatek from the Department of Urology, at the University of Texas Health San Antonio (UTHSA), in San Antonio, United States said "Examination of the phenotype and prognostic significance of intratumoral lymphocytes has led to important insights into disease immunopathogenesis and responses to immunotherapies."

"Examination of the phenotype and prognostic significance of intratumoral lymphocytes has led to important insights into disease immunopathogenesis and responses to immunotherapies."

- Dr. Robert S. Svatek, Department of Urology, at the University of Texas Health San Antonio (UTHSA)

Here, an unbiased examination of bladder tumor-infiltrating cells revealed a relative abundance of natural killer cells among lymphocytes, prompting further examination of their significance in BC. The presence of intratumoral cytotoxic CD8+ T cells is associated with an improved prognosis in both non-muscle invasive and muscle invasive BC , implicating these cells in BC control.

Figure 4: Intratumoral CD56^bright NK cells are more functional than CD56^dim NK cells and correlate with survival in bladder cancer. Bladder intratumoral NK cells were characterized as CD56^bright and CD56^dim populations using flow cytometry. (A) Proportion of NK cells with cytokine or perforin production was identified by flow cytometry. IFN-γ⁺ and TNF-α⁺ cells are shown as a percentage of CD56^bright or CD56^dim NK cells. p-values represent two-tailed unpaired t-test. (B) in vitro cytotoxicity assay of intratumoral NK cells sorted from human bladder tumor tissue against K562. % cell death for CD56^bright and CD56^dim subsets were calculated for 6 representative patients. p-value represents paired two-tailed t test. Kaplan-Meier plots of (C) cancer specific survival (CSS) and (D) overall survival (OS) of bladder cancer patients according to intratumoral CD56^bright and CD56^dim NK cells. p-values represent log-rank (Mantel-Cox) test.

NK cells have been classically described as innate immune effector cells involved in the first line of defense against infections and tumors due to their ability to destroy target cells without antigen priming.

By including patients with both non-muscle invasive and muscle-invasive BC, the study is less homogenous but captures a broad spectrum of disease risk.

The Svatek research team concluded, in their Oncotarget Research Article, "The study is subject to inherent challenges to acquisition of tissue from patients undergoing surgery, including variability in surgical technique and time between tissue removal and processing, which could systematically influence the lymphocyte content and function."

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DOI - https://doi.org/10.18632/oncotarget.26362

Full text - https://www.oncotarget.com/article/26362/text/

Correspondence to - Robert S. Svatek - svatek@uthscsa.edu

Keywords - bladder cancer, NK cells, tumor-infiltrating lymphocytes, CD56, survival

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