Inhibition of the CCR6-CCL20 axis prevents regulatory T cell recruitment and sensitizes head and neck squamous cell carcinoma to radiation therapy

Rutihinda, Cleopatra; Haroun, Ryma; Saidi, Nour Elhouda; Ordoñez, Juan Pablo; Naasri, Sahar; Lévesque, Dominique; Boisvert, François‐Michel; Fortier, Pierre-Hugues; Belzile, Mathieu; Fradet, Laurent; Hubert-Tremblay, Vincent; Turgeon, Guy-Anne; Wang, Chang Shu; Delage, Patrick; Rousseau, Éric; Paquette, Benoît; Oweida, Ayman

doi:10.1007/s00262-022-03313-2

Cited by 22 publications

(14 citation statements)

References 49 publications

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“…Ayman et al [78] showed that mice with Tregs removed via anti-CD25 treatment had enhanced T-cell toxicity, signi cantly delayed tumor growth, and prolonged survival time following radiotherapy compared to those of the radiotherapy-alone group, suggesting that Treg removal enhances the therapeutic effect of radiotherapy. Similarly, another study demonstrated that inhibition of the CCR6-CCL20 axis prevented Treg in ltration and sensitized tumors to radiation therapy [75]. In the present study, the Treg-centered PS construct interacted with radiotherapy, with a signi cantly different effect of the PS on the prognosis of patients according to whether or not they received radiotherapy.…”

Section: Discussionsupporting

confidence: 61%

“…Previous studies have demonstrated that targeting Treg inhibition in various tumors, including breast, colorectal, and head and neck cancers, in combination with radiotherapy, promotes radiotherapy sensitivity [74][75][76] and inhibits radiotherapy resistance. Kesarwani et al [77] found that radiotherapy can signi cantly increase Treg in ltration by altering tryptophan metabolism, creating a more inhibitory immune microenvironment and affecting the e cacy of radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

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Machine learning-based pathomics model to predict the infiltration of regulatory T cells and prognosis in isocitrate dehydrogenase-wild- type glioblastoma

Peng,

Wang,

Chen

et al. 2023

Preprint

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Purpose Regulatory T cells (Tregs) have been highlighted as prognostic factors in isocitrate dehydrogenase (IDH)-wild-type (wt) glioblastoma (GBM). However, conventional detection of Tregs with immunohistochemistry is limited for practical application in clinical settings. The aim of this study was to construct a pathomics model to predict Treg infiltration in IDH-wt GBM and explore the related biological processes. Methods Using the Pyradiomics package, pathomics features were extracted from hematoxylin and eosin-stained biopsy images of patients from The Cancer Genome Atlas. The proportion of Tregs was confirmed in orthotopic glioblastoma mouse model via flow cytometry. The pathomics model was constructed using a gradient-boosting machine-learning approach, and the pathomics score (PS) was determined with the minimal redundancy-maximal relevance and relief algorithms. Cox proportional hazard regression analysis was employed to access the association between PS and overall survival (OS). Transcriptomic data were analyzed through GSEA set enrichment, differential gene expression, and correlation analyses. Results PS was positively correlated with high Treg expression. Patients with a high PS had significantly worse overall survival than did those with a low PS. A high PS independently served as a prognostic risk factor for patients with IDH-wt GBM. Gene set enrichment analysis revealed significant associations between PS and the Notch and IL-6/JAK/STAT3 signaling pathways. A high PS was also significantly correlated with elevated RAD50 expression. Conclusion The developed pathomics model based on machine-learning algorithms can offer an alternative non-invasive method to predict Treg infiltration and prognosis in patients with IDH-wt GBM, further suggesting potential targets for immunotherapy.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Machine learning-based pathomics model to predict the infiltration of regulatory T cells and prognosis in isocitrate dehydrogenase-wild- type glioblastoma

Peng,

Wang,

Chen

et al. 2023

Preprint

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“…When CCL20 is secreted in tumor tissues [ 64 ], it attracts CCR6-expressing Treg cells [ 65 ], which are involved in tumor progression and poor prognosis [ 66 , 67 ]. Therefore, novel cancer treatment strategies using CCR6-expressing chimeric antigen receptor-T (CAR-T) cells have been designed [ 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of the Binding Epitope of an Anti-Mouse CCR6 Monoclonal Antibody (C6Mab-13) Using 1× Alanine Scanning

et al. 2023

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CC chemokine receptor 6 (CCR6) is one of the members of the G-protein-coupled receptor (GPCR) family that is upregulated in many immune-related cells, such as B lymphocytes, effector and memory T cells, regulatory T cells, and immature dendritic cells. The coordination between CCR6 and its ligand CC motif chemokine ligand 20 (CCL20) is deeply involved in the pathogenesis of various diseases, such as cancer, psoriasis, and autoimmune diseases. Thus, CCR6 is an attractive target for therapy and is being investigated as a diagnostic marker for various diseases. In a previous study, we developed an anti-mouse CCR6 (mCCR6) monoclonal antibody (mAb), C6Mab-13 (rat IgG1, kappa), that was applicable for flow cytometry by immunizing a rat with the N-terminal peptide of mCCR6. In this study, we investigated the binding epitope of C6Mab-13 using an enzyme-linked immunosorbent assay (ELISA) and the surface plasmon resonance (SPR) method, which were conducted with respect to the synthesized point-mutated-peptides within the 1–20 amino acid region of mCCR6. In the ELISA results, C6Mab-13 lost its ability to react to the alanine-substituted peptide of mCCR6 at Asp11, thereby identifying Asp11 as the epitope of C6Mab-13. In our SPR analysis, the dissociation constants (KD) could not be calculated for the G9A and D11A mutants due to the lack of binding. The SPR analysis demonstrated that the C6Mab-13 epitope comprises Gly9 and Asp11. Taken together, the key binding epitope of C6Mab-13 was determined to be located around Asp11 on mCCR6. Based on the epitope information, C6Mab-13 could be useful for further functional analysis of mCCR6 in future studies.

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“…When CCL20 is secreted in tumor tissues, it attracts CCR6-expressing Treg cells [50], which are involved in tumor progression and poor prognosis in patients with hepatocellular carcinoma [51]. Using this biological response of CCR6, novel cancer treatment strategies using CCR6-expressing chimeric antigen receptor-T (CAR-T) cells were designed [52,53].…”

Section: Discussionmentioning

confidence: 99%

Identification of the Binding Epitope of an Anti-Mouse CCR6 Monoclonal Antibody (C6Mab-13) Using 1×Alanine Scanning

Tanaka¹,

Tawara²,

Suzuki³

et al. 2023

Preprint

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CC chemokine receptor 6 (CCR6) is one of the members of G protein-coupled receptor (GPCR) family that is upregulated in many immune-related cells, including B lymphocytes, effector and memory T cells, regulatory T cells, and immature dendritic cells. Coordination between CCR6 and its ligand CC motif chemokine ligand 20 (CCL20) is deeply involved in the pathogenesis of various diseases, such as cancer, autoimmune diseases, and psoriasis. Therefore, CCR6 is an attractive target for therapy and is being investigated as a diagnostic marker for patients. In a previous study, we developed an anti-mouse CCR6 (mCCR6) monoclonal antibody (mAb), C6Mab-13 (rat IgG1, kappa), applicable for flow cytometry by immunizing a rat with N-terminal peptide of mCCR6. This study investigated the binding epitope of C6Mab-13 using enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) methods with the synthesized point mutated-peptides within 1-20 amino acids region of mCCR6. In ELISA, C6Mab-13 lost the reaction to the alanine-substituted peptide of D11A. The epitope of C6Mab-13 was identified to be Asp11 in ELISA. Furthermore, in SPR analysis, the dissociation constants (KD) could not be calculated for G9A and D11A mutants due to lack of binding. The SPR analysis demonstrated that the C6Mab-13 epitope comprises Gly9 and Asp11. Taken together, the key binding epitope of C6Mab-13 was determined to be around Asp11 on mCCR6. Based on the epitope information, C6Mab-13 could be useful for further functional analysis of mCCR6 in future studies.

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Inhibition of the CCR6-CCL20 axis prevents regulatory T cell recruitment and sensitizes head and neck squamous cell carcinoma to radiation therapy

Cited by 22 publications

References 49 publications

Machine learning-based pathomics model to predict the infiltration of regulatory T cells and prognosis in isocitrate dehydrogenase-wild- type glioblastoma

Machine learning-based pathomics model to predict the infiltration of regulatory T cells and prognosis in isocitrate dehydrogenase-wild- type glioblastoma

Identification of the Binding Epitope of an Anti-Mouse CCR6 Monoclonal Antibody (C6Mab-13) Using 1× Alanine Scanning

Identification of the Binding Epitope of an Anti-Mouse CCR6 Monoclonal Antibody (C6Mab-13) Using 1×Alanine Scanning

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