Colon-specific immune microenvironment regulates cancer progression versus rejection - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue OncoImmunology Année : 2020

Colon-specific immune microenvironment regulates cancer progression versus rejection

Nathalie Vergnolle
  • Fonction : Auteur
  • PersonId : 1203198

Résumé

Immunotherapies have achieved clinical benefit in many types of cancer but remain limited to a subset of patients in colorectal cancer (CRC). Resistance to immunotherapy can be attributed in part to tissuespecific factors constraining antitumor immunity. Thus, a better understanding of how the colon microenvironment shapes the immune response to CRC is needed to identify mechanisms of resistance to immunotherapies and guide the development of novel therapeutics. In an orthotopic mouse model of MC38-CRC, tumor progression was monitored by bioluminescence imaging and the immune signatures were assessed at a transcriptional level using NanoString and at a cellular level by flow cytometry. Despite initial tumor growth in all mice, only 25% to 35% of mice developed a progressive lethal CRC while the remaining animals spontaneously rejected their solid tumor. No tumor rejection was observed in the absence of adaptive immunity, nor when MC38 cells were injected in non-orthotopic locations, subcutaneously or into the liver. We observed that progressive CRC tumors exhibited a protumor immune response, characterized by a regulatory T-lymphocyte pattern, discernible shortly post-tumor implantation, as well as suppressive myeloid cells. In contrast, tumor-rejecting mice presented an early inflammatory response and an antitumor microenvironment enriched in CD8+ T cells. Taken together, our data demonstrate the role of the colon microenvironment in regulating the balance between anti or protumor immune responses. While emphasizing the relevance of the CRC orthotopic model, they set the basis for exploring the impact of the identified signatures in colon cancer response to immunotherapy.
Fichier principal
Vignette du fichier
Colon specific immune microenvironment regulates cancer progression versus rejection.pdf (5.3 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03000701 , version 1 (16-11-2020)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Giulia Trimaglio, Anne-Françoise Tilkin-Mariamé, Virginie Feliu, Françoise Lauzéral-Vizcaino, Marie Tosolini, et al.. Colon-specific immune microenvironment regulates cancer progression versus rejection. OncoImmunology, 2020, 9 (1), pp.1-12. ⟨10.1080/2162402X.2020.1790125⟩. ⟨hal-03000701⟩
40 Consultations
55 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More