The immune system, which has close interactions with the microbiota, plays an anti-tumorigenic role by surveying for and killing cancer cells. In this regard, recent studies found the microbiota to be essential for the success of cancer immunotherapy treatments in mice, while the bacterial effectors remain unknown. We propose an innovative high throughput screening system to isolate microbiota-derived effectors that modulate the ability of immune cells to kill cancer cells. We utilize the mouse CT26 colon carcinoma cell line as target cells and the GSW11 specific CCD2Z T cell hybridoma cell line as the effector cells. Cytotoxicity and T cell activation assays, measured by LDH release and LacZ expression, respectively, were calibrated to both positive and negative controls and in response to an array of perturbations. Bacterial DNA from mouse colon tumors will serve for the generation of metagenomics libraries. We then plan to screen ∼ 30,000 clones and characterize the cellular and immune responses of identified effectors both in tissue cultures and in animals. Finally, we hope that our future results could be taken to the clinic and serve for diagnosis, prognosis and therapeutics.
Citation Format: Lior Lobel, Wendy Garret. Identifying novel effectors of the gut microbiota that modulate cancer cell killing by CTLs using functional metagenomics [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A077.
- ©2016 American Association for Cancer Research.