The Link between the Multiverse of Immune Microenvironments in Metastases and the Survival of Colorectal Cancer Patients

Cancer Cell. 2018 Dec 10;34(6):1012-1026.e3. doi: 10.1016/j.ccell.2018.11.003.

Abstract

Treatment of metastatic colorectal cancer is based upon the assumption that metastases are homogeneous within a patient. We quantified immune cell types of 603 whole-slide metastases and primary colorectal tumors from 222 patients. Primary lesions, and synchronous and metachronous metastases, had a heterogeneous immune infiltrate and mutational diversity. Small metastases had frequently a low Immunoscore and T and B cell score, while a high Immunoscore was associated with a lower number of metastases. Anti-epidermal growth factor receptor treatment modified immune gene expression and significantly increased T cell densities in the metastasis core. The predictive accuracy of the Immunoscore from a single biopsy was superior to the one of programmed cell death ligand 1 (PD-L1). The immune phenotype of the least-infiltrated metastasis had a stronger association with patient outcome than other metastases.

Keywords: Immunoscore; PDL1; T cells; biopsy; cancer; colorectal cancer; metastasis; prediction; tumor microenvironment; tumor-immunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism
  • Cohort Studies
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / immunology
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / immunology
  • Gene Ontology
  • Gene Regulatory Networks
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / drug effects*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • ErbB Receptors