Abstract A11: Tumor-induced immune disorder: the root cause of cancer cachexia and therapeutic target


 It’s well known that tumor growth induces immune system dysfunction, and cancer immunology has been focused on studying anti-tumor immunity, however the impact of the immune dysfunction on health of the host has not been studied. In this study, we investigate the immune system change and its impact on the host under tumor development from tumor establishment to overall health deterioration and death. We identified significant and multifaceted abnormalities of the immune system which triggers cancer cachexia onset and development. Thus, we propose a new term tumor-induced immune disorder (TID) for these abnormalities. We defined the TID by two parameters: multiple inflammatory cytokines expression; loss of balance and normal behavior of immune cells. Furthermore, we took efforts to explore potential treatments to correct the TID. We have identified a novel immunomodulator, i.e., (R)-ketorolac which can suppress expression of multiple inflammatory cytokines, and consistently, it can fully remove symptoms of cancer cachexia. Thus, we established the causative relationship between TID and cachexia. Interestingly cachectic mice treated by (R)-ketorolac are not only cured of cachexia thus avoid imminent death but also tolerate and respond to full dose anti-tumor chemotherapies. These findings have important clinical implications given majority of late-stage cancer patients with cachexia cannot tolerate chemotherapies and other anti-tumor treatments, thus get stuck in the treatment dilemma. Thus, this study points out a new direction to develop cancer immunotherapies by targeting and correcting the TID, which can not only prevent imminent death by curing cancer cachexia, but also provide opportunities for patients to receive and respond to anti-tumor treatments.
 Citation Format: Lingbing Zhang. Tumor-induced immune disorder: the root cause of cancer cachexia and therapeutic target [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A11.