Renal cell carcinoma (RCC) accounts for 80-95 % of kidney tumors, and approximately 30 % of RCC patients have metastatic disease at diagnosis.
Conventional chemotherapy is not effective in patients with metastatic RCC (MRCC); therefore, immunotherapy with interferon-α (IFN-α) has been employed to improve survival. However, the response rate of MRCC to IFN-α therapy is low. We previously reported that a signal transducer and activator 3 (STAT3) polymorphism was a useful diagnostic marker to predict the response to IFN-α therapy in patients with MRCC. Therefore, we hypothesized the inhibition of STAT3 in the addition of IFN-α therapy might be useful. Moreover, the blockage of STAT3 itself has been reported to enhance the antitumor effects. However, because IFN-α is thought to elicit its therapeutic effect via enhancement of an antitumor immune response mediated by lymphocytes that can be activated by IFN-α administrations, it is probable that the suppression of STAT3 in vivo relates to autoimmune disorders. In the present study, we found Y-box binding protein-1 (YB-1) was poorly expressed in T lymphocytes, as compared with cancer tissues. YB-1 was reported to have an important effect on the STAT3 pathway. Suppression of STAT3 by YB-1 inhibition did not seem to enhance the potential risk for autoimmune disorders. Moreover, we found sensitivity to IFN-α was increased by YB-1 suppression, and this suppression did not down-regulate IFN-α activation of T lymphocytes.
Written by:
Takeuchi A, Shiota M, Tatsugami K, Yokomizo A, Kuroiwa K, Dejima T, Tanaka S, Itsumi M, Eto M, Naito S. Are you the author?
Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
Reference: Cancer Immunol Immunother. 2013 Mar;62(3):517-27
doi: 10.1007/s00262-012-1356-8
PubMed Abstract
PMID: 23052245
