| First Author | Chaib M | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 51 | Pages | eadd3231 |
| PubMed ID | 38134280 | Mgi Jnum | J:343766 |
| Mgi Id | MGI:7569883 | Doi | 10.1126/sciadv.add3231 |
| Citation | Chaib M, et al. (2023) Protein kinase C delta regulates mononuclear phagocytes and hinders response to immunotherapy in cancer. Sci Adv 9(51):eadd3231 |
| abstractText | Mononuclear phagocytes (MPs) play a crucial role in tissue homeostasis; however, MPs also contribute to tumor progression and resistance to immune checkpoint blockade (ICB). Targeting MPs could be an effective strategy to enhance ICB efficacy. We report that protein kinase C delta (PKCdelta), a serine/threonine kinase, is abundantly expressed by MPs in human and mouse tumors. PKCdelta(-/-) mice displayed reduced tumor progression compared to wild types, with increased response to anti-PD-1. Tumors from PKCdelta(-/-) mice demonstrated T(H)1-skewed immune response including increased antigen presentation and T cell activation. Depletion of MPs in vivo altered tumor growth in control but not PKCdelta(-/-) mice. Coinjection of PKCdelta(-/-) M2-like macrophages with cancer cells into wild-type mice markedly delayed tumor growth and significantly increased intratumoral T cell activation compared to PKCdelta(+/+) controls. PKCdelta deficiency reprogrammed MPs by activating type I and type II interferon signaling. Thus, PKCdelta might be targeted to reprogram MPs to augment ICB efficacy. |
