Tumor models to assess immune response and tumor-microbiome interactions in colorectal cancer

Pharmacol Ther. 2022 Mar:231:107981. doi: 10.1016/j.pharmthera.2021.107981. Epub 2021 Sep 2.

Abstract

Despite significant advances over the past 2 decades in preventive screening and therapy aimed at improving patient survival, colorectal cancer (CRC) remains the second most common cause of cancer death in the United States. The average 5-year survival rate of CRC patients with positive regional lymph nodes is only 40%, while less than 5% of patients with distant metastases survive beyond 5 years. There is a critical need to develop novel therapies that can improve overall survival in patients with poor prognoses, particularly since 60% of them are diagnosed at an advanced stage. Pertinently, immune checkpoint blockade therapy has dramatically changed how we treat CRC patients with microsatellite-instable high tumors. Furthermore, accumulating evidence shows that changes in gut microbiota are associated with the regulation of host antitumor immune response and cancer progression. Appropriate animal models are essential to deciphering the complex mechanisms of host antitumor immune response and tumor-gut microbiome metabolic interactions. Here, we discuss various mouse models of colorectal cancer that are developed to address key questions on tumor immune response and tumor-microbiota interactions. These CRC models will also serve as resourceful tools for effective preclinical studies.

Keywords: Carcinogenic Model; Colorectal cancer; Humanization; Imaging; Microbiota; Organoids; Orthotopic model; Tumor Immunology.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Colorectal Neoplasms* / drug therapy
  • Gastrointestinal Microbiome*
  • Humans
  • Immunity
  • Mice