CD4 T cells target colorectal cancer antigens upregulated by oxaliplatin.

Fiche publication

Date publication

août 2019

Journal

International journal of cancer

Auteurs

Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier , Dr BOIDOT Romain , Pr BORG Christophe , Dr GODET Yann , Dr ROYER Bernard , Mme LAHEURTE Caroline , Dr GALAINE Jeanne , Dr LAKKIS Zaher , Dr LOYON Romain

Tous les auteurs :
Galaine J, Turco C, Vauchy C, Royer B, Mercier-Letondal P, Queiroz L, Loyon R, Mouget V, Boidot R, Laheurte C, Lakkis Z, Jary M, Adotévi O, Borg C, Godet Y

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/31396953

Résumé

Immune checkpoint blockade has proven its efficacy in hypermutated subtypes of metastatic colorectal cancers (mCRC). Immunogenic potential can also be observed with conventional chemotherapies, but this property has never been explored thoroughly in CRC patients. The CRC therapeutic arsenal includes oxaliplatin, a well-characterized platinum drug already described as immunogenic. Here, we investigated the impact of the oxaliplatin-based treatment on mCRC immunopeptidome. We demonstrated that oxaliplatin-resistant colorectal cancer cell lines overexpressed Telomerase Reverse Transcriptase (TERT), Colorectal-associated-tumor Antigen-1 (COA-1) and mesothelin tumor associated antigens. We identified new HLA class-II-restricted and promiscuous peptides derived from COA-1 and mesothelin. The two naturally processed peptides COA-1 and Meso appear to be the most immunogenic in mCRC patients. A prospective cohort of 162 mCRC patients enabled us to explore the impact of oxaliplatin exposure on the antitumor-specific immune response. Interestingly, chemotherapy-naive mCRC patients present high immune CD4 T cell responses directed against TERT, COA-1 and mesothelin-derived peptides. These antitumor T cells responses were maintained after 3 months of oxaliplatin-based treatment. Altogether, these findings highlight the interest of immunostimulatory agents to improve the management of chemoresistant mCRC patients. Finally, the high frequency of immune responses targeting the new immunogenic peptides derived from COA-1 and mesothelin support their use in immunomonitoring strategies. This article is protected by copyright. All rights reserved.