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

Document Type

Article

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

Area of Special Interest

Cancer

Specialty/Research Institute

Oncology

DOI

10.1038/s41598-023-35834-w