CCL22-based peptide vaccines induce anti-cancer immunity by modulating tumor microenvironment.

Autor:	Lecoq I; Department of Research and Development, IO Biotech ApS, Copenhagen, Denmark.; National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark., Kopp KL; Department of Research and Development, IO Biotech ApS, Copenhagen, Denmark., Chapellier M; Department of Research and Development, IO Biotech ApS, Copenhagen, Denmark., Mantas P; Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark., Martinenaite E; Department of Research and Development, IO Biotech ApS, Copenhagen, Denmark.; National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark., Perez-Penco M; National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark., Rønn Olsen L; Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark., Zocca MB; Department of Research and Development, IO Biotech ApS, Copenhagen, Denmark., Wakatsuki Pedersen A; Department of Research and Development, IO Biotech ApS, Copenhagen, Denmark., Andersen MH; National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2022 Aug 29; Vol. 11 (1), pp. 2115655. Date of Electronic Publication: 2022 Aug 29 (Print Publication: 2022).
DOI:	10.1080/2162402X.2022.2115655
Abstrakt:	CCL22 is a macrophage-derived immunosuppressive chemokine that recruits regulatory T cells through the CCL22:CCR4 axis. CCL22 was shown to play a key role in suppressing anti-cancer immune responses in different cancer types. Recently, we showed that CCL22-specific T cells generated from cancer patients could kill CCL22-expressing tumor cells and directly influence the levels of CCL22 in vitro . The present study aimed to provide a rationale for developing a CCL22-targeting immunotherapy. Vaccination with CCL22-derived peptides induced CCL22-specific T-cell responses in both BALB/c and C57BL/6 mice, assessed by interferon-γ secretion ex vivo . Anti-tumor efficacy of the peptides was evaluated in mouse models engrafted with syngeneic tumor models showing a reduced tumor growth and prolonged survival of the treated mice. Vaccination induced changes in the cellular composition of immune cells that infiltrated the tumor microenvironment assessed with multicolor flow cytometry. In particular, the infiltration of CD8 + cells and M1 macrophages increased, which increased the CD8/Treg and the M1/M2 macrophage ratio. This study provided preclinical evidence that targeting CCL22 with CCL22 peptide vaccines modulated the immune milieu in the tumor microenvironment. This modulation led to an augmentation of anti-tumor responses. This study provided a rationale for developing a novel immunotherapeutic modality in cancer. Competing Interests: ILM, KLK, MC, EM and AWP are employed by IO Biotech. M-BZ is an employee and a shareholder in IO Biotech. MHA is Founder, a shareholder and a Scientific Advisory Board member in IO Biotech. The other authors declare no direct conflicts of interest. (© 2022 IO Biotech ApS. Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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