Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

Francesca Bergomas,Samantha Pesce,Paola Allavena,Andrea Doni,Luigi Laghi,Federica Marchesi,Alberto Mantovani,Fabio Grizzi

doi:10.3390/cancers4010001

Francesca Bergomas, Samantha Pesce + Show 6 more

Open Access

https://doi.org/10.3390/cancers4010001

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Abstract

Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

Highlights

Immune responses can develop independently of secondary lymphoid organs, in tertiary lymphoid tissue, which develops ectopically at sites of inflammation or infection in peripheral, non-lymphoid organs [1,2,3]
We found that tumor infiltrating lymphocytes are scattered throughout the stroma and interspersed between tumor cells (Figure 1D); they cluster in aggregates resembling tertiary lymphoid tissue (Figure 1B,C)
The importance of defining the presence of tertiary lymphoid tissue at the tumor site arises from the possibility of an organized immune response taking place in the follicles and possibly controlling tumor invasion and metastasis

Summary

Introduction

Immune responses can develop independently of secondary lymphoid organs, in tertiary lymphoid tissue (or organs), which develops ectopically at sites of inflammation or infection in peripheral, non-lymphoid organs [1,2,3] In these pathologic settings, tissues harboring target antigens are infiltrated by cellular effectors of the immune system, which organize anatomically and functionally as in secondary lymphoid organs (lymph nodes, spleen), with formation of B-cell follicles and T-cell areas. Tissues harboring target antigens are infiltrated by cellular effectors of the immune system, which organize anatomically and functionally as in secondary lymphoid organs (lymph nodes, spleen), with formation of B-cell follicles and T-cell areas The possibility that these organized lymphoid aggregates behave as functional immune sites for. Whether B and T lymphocytes infiltrating human colon cancer organize in lymphoid structures, potentially contributing to their immune activation is still unknown

Ectopic Lymphoid Tissue is Present in the Mucosa of Colon-Cancer Patients

Patients

Immunohistochemistry

Immunofluorescence

Morphometric Analysis

Conclusions