Spatial and phenotypic immune profiling of metastatic colon cancer Journal Article

Authors: Lazarus, J.; Maj, T.; Smith, J. J.; Perusina Lanfranca, M.; Rao, A.; D'Angelica, M. I.; Delrosario, L.; Girgis, A.; Schukow, C.; Shia, J.; Kryczek, I.; Shi, J.; Wasserman, I.; Crawford, H.; Nathan, H.; Pasca Di Magliano, M.; Zou, W.; Frankel, T. L.
Article Title: Spatial and phenotypic immune profiling of metastatic colon cancer
Abstract: Paramount to the efficacy of immune checkpoint inhibitors is proper selection of patients with adequate tumor immunogenicity and a robust but suppressed immune infiltrate. In colon cancer, immune-based therapies are approved for patients with DNA mismatch repair (MMR) deficiencies, in whom accumulation of genetic mutations results in increased neoantigen expression, triggering an immune response that is suppressed by the PD-L1/PD-1 pathway. Here, we report that characterization of the microenvironment of MMR-deficient metastatic colorectal cancer using multiplex fluorescent immunohistochemistry (mfIHC) identified increased infiltration of cytotoxic T lymphocytes (CTLs), which were more often engaged with epithelial cells (ECs) and improved overall survival. A subset of patients with intact MMR but a similar immune microenvironment to MMR-deficient patients was identified and found to universally express high levels of PD-L1, suggesting that they may represent a currently untreated, checkpoint inhibitor-responsive population. Further, PD-L1 expression on antigen-presenting cells (APCs) in the tumor microenvironment (TME) resulted in impaired CTL/EC engagement and enhanced infiltration and engagement of Tregs. Characterization of the TME by mfIHC highlights the interconnection between immunity and immunosuppression in metastatic colon cancer and may better stratify patients for receipt of immunotherapies.
Keywords: colorectal cancer; cancer immunotherapy; oncology; immunology; cancer
Journal Title: JCI Insight
Volume: 3
Issue: 22
ISSN: 2379-3708
Publisher: Amer Soc Clinical Investigation Inc  
Date Published: 2018-11-15
Start Page: e121932
Language: English
DOI: 10.1172/jci.insight.121932
PUBMED: 30429368
PROVIDER: scopus
PMCID: PMC6302940
Notes: Source: Scopus
Citation Impact
MSK Authors
  1. Jinru Shia
    542 Shia
  2. Jesse Joshua Smith
    78 Smith