Sunitinib does not impair natural killer cell function in patients with renal cell carcinoma

Abstract

Abstract. Although the available treatment options have expanded, the survival of patients with metastatic renal cell carcinoma (RCC) remains poor. As patients with RCC lack responsiveness to chemotherapy or radiation, therapeutic options predominantly include surgical interventions and immunomodulatory approaches, including the administration of tyrosine kinase inhibitors (TKIs) such as sunitinib. Natural killer (NK) cells have been reported to be key players in TKI-mediated off-target effects on the immune system. However, only limited information is available regarding the possible impact of sunitinib on the function of NK cells of individual patients. The present study reports on the immunomonitoring results of three patients with metastatic RCC who underwent sunitinib treatment. These results were compared with age-matched, healthy controls in terms of the immune status of T, B and NK cells, focusing on functional in vitro analyses of NK cells. In all three patients, NK cell number, subset distribution and function, as measured by cluster of differentiation 107a degranulation, did not exhibit any significant alterations as a result of sunitinib treatment. These results indicate that sunitinib does not negatively affect NK cell function, which supports the pursuit of therapeutic modalities that combine immunomodulation and NK cell-stimulating approaches.

An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors

“…Reassuringly, most designated neutrophils, macrophages, and eosinophils were found in the myeloid pool and most designated T cells, NK cells, and B cells were found in the lymphoid pool. Moreover, most lymphoid cells were designated as T cells, which is consistent with previous reports of counts of lymphoid cells in RCC (32). Admittedly, technical issues may exist that led to some apparent artefacts, such as assignment of some B cells in the myeloid pool.…”

NK Cell-Based Immunotherapy in Renal Cell Carcinoma

“…For example, resting and IL-2 activated NK cells exhibited less degranulation and cytokine production when exposed to pharmacological doses of sorafenib, but not sunitinib, in a mechanism involving impaired PI3K and ERK phosphorylation [164]. Other studies have also shown that sunitinib does not impair NK cell function in patients with RCC [165]. On the other hand, sunitinib has been found to induce the expression of MICA, MICB, and ULBP1-3, all of them ligands of the activating NKG2D receptor, on nasopharyngeal cancer cell lines that lead to an increase in their susceptibility to NK cell-mediated cytoxicity [166].…”