TY - JOUR

T1 - CCL22-based peptide vaccines induce anti-cancer immunity by modulating tumor microenvironment

AU - Lecoq, Inés

AU - Kopp, Katharina L.

AU - Chapellier, Marion

AU - Mantas, Panagiotis

AU - Martinenaite, Evelina

AU - Perez-Penco, Maria

AU - Rønn Olsen, Lars

AU - Zocca, Mai Britt

AU - Wakatsuki Pedersen, Ayako

AU - Andersen, Mads Hald

N1 - Publisher Copyright: © 2022 IO Biotech ApS. Published with license by Taylor & Francis Group, LLC.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - CCL22

KW - immune modulation

KW - immunotherapy

KW - peptide vaccine

KW - tumor microenvironment

U2 - 10.1080/2162402X.2022.2115655

DO - 10.1080/2162402X.2022.2115655

M3 - Journal article

C2 - 36052217

AN - SCOPUS:85136873600

VL - 11

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 1

M1 - 2115655

ER -