Santegoets SJ, Turksma AW, Powell DJ, Hooijberg E, de Gruijl TD. IL-21 in cancer immunotherapy: at the right place at the right time. Oncoimmunology. 2013;2: e24522.

Article  PubMed  PubMed Central  Google Scholar 

Leonard WJ, Lin JX, O’Shea JJ. The γc family of cytokines: basic biology to therapeutic ramifications. Immunity. 2019;50(4):832–50.

Article  CAS  PubMed  Google Scholar 

Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, et al. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 1993;73(1):147–57.

Article  CAS  PubMed  Google Scholar 

Habib T, Senadheera S, Weinberg K, Kaushansky K. The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3. Biochemistry. 2002;41(27):8725–31.

Article  CAS  PubMed  Google Scholar 

Berglund LJ, Avery DT, Ma CS, Moens L, Deenick EK, Bustamante J, et al. IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts. Blood. 2013;122(24):3940–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leonard WJ, Wan C-K. IL-21 signaling in immunity. F1000Res. 2016;5:F1000 Faculty Rev-224.

Article  PubMed  PubMed Central  Google Scholar 

Davis MR, Zhu Z, Hansen DM, Bai Q, Fang Y. The role of IL-21 in immunity and cancer. Cancer Lett. 2015;358:107–14.

Article  CAS  PubMed  Google Scholar 

Tanabe Y, Nishibori T, Su L, Arduini RM, Baker DP, David M. Cutting edge: role of STAT1, STAT3, and STAT5 in IFN-alpha beta responses in T lymphocytes. J Immunol. 2005;174:609–13.

Article  CAS  PubMed  Google Scholar 

Matsuoka T, Yashiro M. The role of PI3K/Akt/mTOR signaling in gastric carcinoma. Cancers (Basel). 2014;6:1441–63.

Article  CAS  PubMed  Google Scholar 

Waskiewicz AJ, Cooper JA. Mitogen and stress response pathways: MAP kinase cascades and phosphatase regulation in mammals and yeast. Curr Opin Cell Biol. 1995;7:798–805.

Article  CAS  PubMed  Google Scholar 

Chabab G, Bonnefoy N, Lafont V. IL-21 signaling in the tumor microenvironment. Adv Exp Med Biol. 2020;1240:73–82.

Article  CAS  PubMed  Google Scholar 

Ferrari-Lacraz S, Chicheportiche R, Schneiter G, Molnarfi N, Villard J, Dayer JM. IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes. Int Immunol. 2008;20(8):1009–18.

Article  CAS  PubMed  Google Scholar 

Deenick EK, Avery DT, Chan A, Berglund LJ, Ives ML, Moens L, et al. Naive and memory human B cells have distinct requirements for STAT3 activation to differentiate into antibody-secreting plasma cells. J Exp Med. 2013;210(12):2739–53.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang T, Zhou C, Ren S. Role of IL-2 in cancer immunotherapy. Oncoimmunology. 2016;5: e1163462.

Article  PubMed  PubMed Central  Google Scholar 

Rosenberg SA. IL-2: the first effective immunotherapy for human cancer. J Immunol. 2014;192:5451–8.

Article  CAS  PubMed  Google Scholar 

Li Y, Yee C. IL-21 mediated Foxp3 suppression leads to enhanced generation of antigen-specific CD8+ cytotoxic T lymphocytes. Blood. 2008;111:229–35.

Article  PubMed  PubMed Central  Google Scholar 

Propper DJ, Balkwill FR. Harnessing cytokines and chemokines for cancer therapy. Nat Rev Clin Oncol. 2022;19(4):237–53.

Article  CAS  PubMed  Google Scholar 

Moudgil KD, Choubey D. Cytokines in autoimmunity: role in induction, regulation, and treatment. J Interferon Cytokine Res. 2011;31(10):695–703.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma HL, Whitters MJ, Konz RF, Senices M, Young DA, Grusby MJ, et al. IL-21 activates both innate and adaptive immunity to generate potent antitumor responses that require perforin but are independent of IFN-gamma. J Immunol. 2003;171(2):608–15.

Article  CAS  PubMed  Google Scholar 

Ugai S, Shimozato O, Yu L, Wang YQ, Kawamura K, Yamamoto H, et al. Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects. Cancer Gene Ther. 2003;10(10):771–8.

Article  CAS  PubMed  Google Scholar 

Zeng R, Spolski R, Casas E, Zhu W, Levy DE, Leonard WJ. The molecular basis of IL-21-mediated proliferation. Blood. 2007;109(10):4135–42.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Davis ID, Skak K, Smyth MJ, Kristjansen PE, Miller DM, Sivakumar PV. Interleukin-21 signaling: functions in cancer and autoimmunity. Clin Cancer Res. 2007;13(23):6926–32.

Article  CAS  PubMed  Google Scholar 

Corvinus FM, Orth C, Moriggl R, Tsareva SA, Wagner S, Pfitzner EB, et al. Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth. Neoplasia. 2005;7(6):545–55.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rahaman SO, Harbor PC, Chernova O, Barnett GH, Vogelbaum MA, Haque SJ. Inhibition of constitutively active Stat3 suppresses proliferation and induces apoptosis in glioblastoma multiforme cells. Oncogene. 2002;21(55):8404–13.

Article  CAS  PubMed  Google Scholar 

Lamprecht B, Kreher S, Anagnostopoulos I, Jöhrens K, Monteleone G, Jundt F, et al. Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3alpha. Blood. 2008;112(8):3339–47.

Article  CAS  PubMed  Google Scholar 

van der Fits L, Out-Luiting JJ, Tensen CP, Zoutman WH, Vermeer MH. Exploring the IL-21-STAT3 axis as therapeutic target for Sézary syndrome. J Invest Dermatol. 2014;134:2639–47.

Article  PubMed  Google Scholar 

Skrombolas D, Frelinger JG. Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy. Expert Rev Clin Immunol. 2014;10(2):207–17.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rallis KS, Corrigan AE, Dadah H, George AM, Keshwara SM, Sideris M, et al. Cytokine-based cancer immunotherapy: challenges and opportunities for IL-10. Anticancer Res. 2021;41(7):3247–52.

Article  PubMed  Google Scholar 

Jenks S. After initial setback, IL-12 regaining popularity. J Natl Cancer Inst. 1996;88:576–7.

Article  CAS  PubMed  Google Scholar 

Wang G, Tschoi M, Spolski R, Lou Y, Ozaki K, Feng C, et al. In vivo antitumor activity of interleukin 21 mediated by natural killer cells. Cancer Res. 2003;63:9016–22.

CAS  PubMed  Google Scholar