Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer
oregon; chiles; Mice; Animals; CD8-Positive T-Lymphocytes; Myeloid Differentiation Factor 88; Monocytes; Pancreatic Neoplasms; Mice, Knockout; Adjuvants, Immunologic; Mice, Inbred C57BL
Radiation therapy induces immunogenic cell death in cancer cells, whereby released endogenous adjuvants are sensed by immune cells to direct adaptive immune responses. TLRs expressed on several immune subtypes recognize innate adjuvants to direct downstream inflammatory responses in part via the adapter protein MyD88. We generated Myd88 conditional knockout mice to interrogate its contribution to the immune response to radiation therapy in distinct immune populations in pancreatic cancer. Surprisingly, Myd88 deletion in Itgax (CD11c)-expressing dendritic cells had little discernable effects on response to RT in pancreatic cancer and elicited normal T cell responses using a prime/boost vaccination strategy. Myd88 deletion in Lck-expressing T cells resulted in similar or worsened responses to radiation therapy compared to wild-type mice and lacked antigen-specific CD8
Medler, Terry R; Blair, Tiffany; Alice, Alejandro F; Dowdell, Alexa K; Piening, Brian D.; Crittenden, Marka R; and Gough, Michael J., "Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer" (2023). Articles, Abstracts, and Reports. 7497.