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Front. Immunol. | doi: 10.3389/fimmu.2019.01884

The Crohn’s-like lymphoid reaction to colorectal cancer - tertiary lymphoid structures with immunologic and potentially therapeutic relevance in colorectal cancer

 Asaf Maoz1*,  Michael Dennis1 and Joel K. Greenson2
  • 1School of Medicine, Boston University, United States
  • 2Department of Pathology, School of Medicine, University of Michigan, United States

The Crohn’s-like lymphoid reaction (CLR) to colorectal cancer (CRC), a CRC-specific ectopic lymphoid reaction, is thought to play an important role in the host response to CRC. CLR is characterized by peritumoral lymphocytic aggregates that are found at the advancing edge of the tumor. Spatial and molecular characterization of CLR within the tumor microenvironment (TME) have uncovered a spectrum of peritumoral lymphoid aggregates with varying levels of organization and maturation. In early stages of CLR development, CD4+ T-cells cluster predominantly with mature antigen presenting dendritic cells. As CLR matures, increasing numbers of B-cells, as well as follicular dendritic cells, are recruited to create lymphoid follicles. When highly organized, CLR resembles functional tertiary lymphoid structures (TLS), allowing for lymphocyte recruitment to the TME and promoting a tumor-specific adaptive immune response. CLR has been consistently associated with favorable prognostic factors and improved survival among CRC patients, often providing more prognostic information than current clinical staging systems. However, consensus is lacking regarding CLR scoring and it is not clinically assessed or reported. Differences between CLR and other cancer-associated lymphoid structures exist both in primary and metastatic disease, underscoring the need to characterize organ-specific TLS. Further research is needed to explore the role of CLR in predicting response to immunotherapy and to leverage CLR to promote immunotherapeutic strategies in CRC.

Keywords: Crohn's-like lymphoid reaction, colorectal cancer, adaptive immune response, tumor immunology and microenvironment, microsatellite instability (MSI), Tertiary Lymphoid Structures (TLS), Ectopic lymphoid structure, Tertiary lymphoid organs

Received: 01 Jun 2019; Accepted: 25 Jul 2019.

Edited by:

Khashayarsha Khazaie, Mayo Clinic College of Medicine & Science, United States

Reviewed by:

Subbaya Subramanian, University of Minnesota Twin Cities, United States
Masoud H. Manjili, Massey Cancer Center, Virginia Commonwealth University, United States  

Copyright: © 2019 Maoz, Dennis and Greenson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD. Asaf Maoz, School of Medicine, Boston University, Boston, United States,