Congratulations to our co-founder Prof. Li Tang on the publishing of two Nature papers on the unexpected role of type 2 immunity against cancer!
Thrilled to share our back-to-back two Nature Magazine papers on the unexpected role of type 2 immunity against cancer. We found that interleukin 4 (Fc–IL-4), a type 2 cytokine, reinvigorates exhausted T cells to potentiate anticancer immunotherapy w/ Yugnag Guo Zhejiang University and Rong Fan (1/11) In the second Nature Magazine paper, a long-term clinical study, led by Rong Fan, Stephan Grupp, Carl June, Jan Joseph Melenhorst, and ourselves Li Tang, reveals that type-2 functionality in CAR-T infusion products favours 8-year relapse-free leukaemia remission in patients! (2/11) both papers can be accessed freely: https://lnkd.in/g28pGiYA, https://lnkd.in/gFPsTBMh (3/11) Current cancer immunotherapy predominately focuses on eliciting type 1 immune response against cancer; however, frequent emergence of resistance and relapse suggests that boosting type 1 immunity alone may not be sufficient to elicit durable antitumor effects.(4/11) The two studies, one using preclinical models for understanding how and why, and the other relying on clinical follow-up study, together highlight the remarkable potential of coordinating type 1 and 2 immunity for future development of cancer immunotherapy.(5/11) We first show that Fc–IL-4 combined with type 1-centric ACT and ICB therapies efficiently eliminates solid tumors in multiple syngeneic and xenograft models. Strikingly, all cured mice resisted the secondary rechallenge suggesting induction of long-term memory.(6/11) We further found that Fc–IL-4 specifically enriches the terminally exhausted CD8+ T (CD8+ TTE) in tumor and promotes their effector function. Interestingly, the enrichment of CD8+ TTE induced by Fc–IL-4 was mainly due to alleviated cell apoptosis.(7/11) We next show Fc–IL-4 augments the glycolytic metabolism and increases the NAD concentration of CD8+ TTE cells; LDHA is significantly upregulated by Fc–IL-4 and plays an indispensable role for Fc–IL-4 to improve the metabolism and effector function of CD8+ TTE cells.(8/11) Further mechanistic studies show that Fc–IL-4 signals through both signal transducer and activator of transcription 6 (STAT6) and mammalian target of rapamycin (mTOR) pathways to enhance glycolysis, survival, and effector function of CD8+ TTEcells. (9/11) Both work was led by Bing Feng @bingfen93937241 and Zhiliang Bai @Zhiliang_Bai, two talented postdocs, who will start their own labs soon. We also thank our collaborators and other @Tang_Lab_EPFL lab members, and core facilities - it was a fun team effort! We are grateful for the support from EPFL, EPFL School of Engineering, EPFL School of Life Sciences, @epfl bioengineering, @Materials_EPFL and our funding sources Swiss National Science Foundation SNSF, Krebsliga Schweiz, European Research Council (ERC), XtalPi Inc., #Kristian Gerhard Jebsen Foundation, #Anna Fuller Fund Grant. (11/11)