Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer
Publication Title
Sci Rep
Authors
Terry R Medler, Earle A. Chiles Research Institute, Providence Cancer Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 4805 NE Glisan Street, Suite 2N100, Portland, OR, 97213, USAFollow
Tiffany Blair, Earle A. Chiles Research Institute, Providence Cancer Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 4805 NE Glisan Street, Suite 2N100, Portland, OR, 97213, USAFollow
Alejandro F Alice, Earle A. Chiles Research Institute, Providence Cancer Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 4805 NE Glisan Street, Suite 2N100, Portland, OR, 97213, USAFollow
Alexa K Dowdell, Earle A. Chiles Research Institute, Providence Cancer Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 4805 NE Glisan Street, Suite 2N100, Portland, OR, 97213, USAFollow
Brian D. Piening, Molecular Genomics Laboratory, Providence Portland Medical Center, Portland, OR; Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Cancer Center, Portland, OR.Follow
Marka R Crittenden, Earle A. Chiles Research Institute, Providence Cancer Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 4805 NE Glisan Street, Suite 2N100, Portland, OR, 97213, USAFollow
Michael J. Gough, Earle A. Chiles Research Institute, Providence Cancer Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 4805 NE Glisan Street, Suite 2N100, Portland, OR, 97213, USAFollow
Publication Date
5-27-2023
Keywords
oregon; chiles; Mice; Animals; CD8-Positive T-Lymphocytes; Myeloid Differentiation Factor 88; Monocytes; Pancreatic Neoplasms; Mice, Knockout; Adjuvants, Immunologic; Mice, Inbred C57BL
Abstract
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
Clinical Institute
Cancer
Specialty/Research Institute
Oncology
DOI
10.1038/s41598-023-35834-w
