LTX-315 triggers anticancer immunity by inducing MyD88-dependent maturation of dendritic cells.

Autor:	Li XQ; Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin Medical University, Tianjin, China.; Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States., Yamazaki T; Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, United States., He T; Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States., Alam MM; Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States., Liu J; Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States., Trivett AL; Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States., Sveinbjørnsson B; Lytix Biopharma, Oslo, Norway., Rekdal Ø; Lytix Biopharma, Oslo, Norway., Galluzzi L; Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, United States.; Sandra and Edward Meyer Cancer Center, New York, NY, United States.; Caryl and Israel Englander Institute for Precision Medicine, New York, NY, United States., Oppenheim JJ; Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States., Yang; Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Mar 13; Vol. 15, pp. 1332922. Date of Electronic Publication: 2024 Mar 13 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1332922
Abstrakt:	LTX-315 is a synthetic cationic oncolytic peptide with potent anticancer activity but limited toxicity for non-malignant cells. LTX-315 induces both immunogenic tumor cell death and generation of tumor-specific immune responses in multiple experimental tumor models. Given the central role of dendritic cell (DC) maturation in the induction of antigen-specific immunity, we investigated the effect of LTX-315 treatment on the maturation of tumor-infiltrating DCs (TiDCs) and the generation of anti-melanoma immunity. We found that LTX-315 treatment induces the maturation of DCs, both indirectly through the release of cancer cell-derived damage-associated molecular patterns (DAMPs)/alarmins and nucleic acids (DNA and RNA) capable of triggering distinct Toll-like receptor (TLR) signaling, and, directly by activating TLR7. The latter results in the ignition of multiple intracellular signaling pathways that promotes DC maturation, including NF-κB, mitogen activated protein kinases (MAPKs), and inflammasome signaling, as well as increased type 1 interferon production. Critically, the effects of LTX-315 on DCs the consequent promotion of anti-melanoma immunity depend on the cytosolic signal transducer myeloid differentiation response gene 88 (MyD88). These results cast light on the mechanisms by which LTX-315 induces DC maturation and hence elicits anticancer immunity, with important implications for the use of LTX-315 as an anticancer immunotherapeutic. Competing Interests: BS and ØR are shareholders and employed by Lytix Biopharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received some funding from Lytix Biopharma. As employees of Lytix Biopharma, BS and ØR provided LTX-315 for this study and assisted in reviewing & editing of the graphic abstract & manuscript. (Copyright © 2024 Li, Yamazaki, He, Alam, Liu, Trivett, Sveinbjørnsson, Rekdal, Galluzzi, Oppenheim and Yang.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu