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

Inés Lecoq, Katharina L. Kopp, Marion Chapellier, Panagiotis Mantas, Evelina Martinenaite, Maria Perez-Penco, Lars Rønn Olsen, Mai Britt Zocca, Ayako Wakatsuki Pedersen*, Mads Hald Andersen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.

Original languageEnglish
Article number2115655
JournalOncoImmunology
Volume11
Issue number1
Number of pages12
ISSN2162-4011
DOIs
Publication statusPublished - 2022

Keywords

  • CCL22
  • Immune modulation
  • Immunotherapy
  • Peptide vaccine
  • Tumor microenvironment

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