Association of Myeloid-derived Suppressor Cells and Efficacy of Cytokine-induced Killer Cell Immunotherapy in Metastatic Renal Cell Carcinoma Patients

Abstract

Metastatic renal cell carcinoma (MRCC) is one of the malignancies that are sensitive to immunotherapy. However, the underlying immune inhibitory factors such as myeloid-derived suppressor cells (MDSCs) might restrain the efficacy of immunotherapy. The present study investigates the clinical efficacy of cytokine-induced killer (CIK) cell therapy in patients with MRCC and explores whether the levels of peripheral MDSCs are associated with the prognosis of patients receiving this therapy. Twenty-nine patients with measurable MRCC were treated with an adoptive transfer of autologous CIK cells, followed by 5 consecutive days of interleukin-2 administration. The tumor response and 1-year survival were observed. The proportion of MDSCs in the peripheral blood was detected, and the correlation of MDSCs with prognosis was analyzed. Of 29 evaluable patients, no complete responses were seen; 4 patients exhibited a partial response (13.8%), 18 patients displayed stable disease (62.1%), and 7 patients showed progressive disease (24.1%). Twenty patients (69.0%) were alive 14.8-41.4 months at the time of the last follow-up (median follow-up=20.2 mo). The 1-year survival was 82.8% (24/29). Peripheral blood MDSCs were elevated in almost all MRCC patients and decreased after CIK-cell infusion. Subgroup analysis indicated that patients with a relatively low proportion of MDSCs exhibited prolonged survival. In conclusion, our data suggest that transfusion of autologous CIK cells can induce regression of MRCC, and MDSCs can serve as a potential marker for the prognosis of patients receiving a CIK-based therapy.

Efficacy of RetroNectin-activated cytokine-induced killer cell therapy in the treatment of advanced hepatocelluar carcinoma

“…Recent studies have reported that RetroNectin can improve conglutination, extension, differentiation and proliferation of cultured cells, all of which contribute to more efficient stimulation of T cells (21)(22)(23)(24). Our previous study also confirmed this (25). In the present study, the clinical effects of R-CIK therapy were compared with standard chemotherapy and the predictive factors governing the efficacy of R-CIK treatment were investigated in patients with advanced HCC.…”

“…RetroNectin (RN) was added to the culture media in our CIK cell preparation (called R-CIK), which improves the conglutination, extension, and differentiation of these cells (25). Our results indicate that the percentages of CD3+, CD3+/CD4+, CD3+/CD8+ and CD3+/CD56+ cells were significantly increased after stimulation and expansion in culture (25). In addition, there was a significant decrease in the CD3-/CD16+/CD56+ population.…”

“…In the CIK cell preparations in the present study, the method of culture was slightly different from methods employed in previous literature and it was possible to obtain more of the CD3+/CD56+ cellular subset on day 15 than common CIK cells preparation methods achieve (28). RetroNectin (RN) was added to the culture media in our CIK cell preparation (called R-CIK), which improves the conglutination, extension, and differentiation of these cells (25). Our results indicate that the percentages of CD3+, CD3+/CD4+, CD3+/CD8+ and CD3+/CD56+ cells were significantly increased after stimulation and expansion in culture (25).…”

“…CD3+/CD56+ cells, which comprise a rare population of cells in normal peripheral blood, are also significantly increased after stimulation and expansion. These may be the most important cells for the anti-cancer effect of CIK treatment (36) as they have shown strong anti-cancer activity in a variety of malignant tumor cell lines in vitro (20,25,37). Therefore, we have good reason to hypothesize that our improved methods have allowed us to obtain R-CIK cells with particularly strong anti-tumor activity for transferring them to patients.…”

“…The method used for CIK cell preparation in the present study was slightly different from methods detailed in previous literature (25,28). Peripheral blood mononuclear cells (PBMCs) were collected from 50 ml peripheral blood draws taken from patients.…”