TY - JOUR

T1 - Immune Modulatory Properties of Collagen in Cancer

AU - Rømer, Anne Mette Askehøj

AU - Thorseth, Marie Louise

AU - Madsen, Daniel Hargbøl

N1 - Publisher Copyright: Copyright © 2021 Rømer, Thorseth and Madsen.

PY - 2021

Y1 - 2021

N2 - During tumor growth the extracellular matrix (ECM) undergoes dramatic remodeling. The normal ECM is degraded and substituted with a tumor-specific ECM, which is often of higher collagen density and increased stiffness. The structure and collagen density of the tumor-specific ECM has been associated with poor prognosis in several types of cancer. However, the reason for this association is still largely unknown. Collagen can promote cancer cell growth and migration, but recent studies have shown that collagens can also affect the function and phenotype of various types of tumor-infiltrating immune cells such as tumor-associated macrophages (TAMs) and T cells. This suggests that tumor-associated collagen could have important immune modulatory functions within the tumor microenvironment, affecting cancer progression as well as the efficacy of cancer immunotherapy. The effects of tumor-associated collagen on immune cells could help explain why a high collagen density in tumors is often correlated with a poor prognosis. Knowledge about immune modulatory functions of collagen could potentially identify targets for improving current cancer therapies or for development of new treatments. In this review, the current knowledge about the ability of collagen to influence T cell activity will be summarized. This includes direct interactions with T cells as well as induction of immune suppressive activity in other immune cells such as macrophages. Additionally, the potential effects of collagen on the efficacy of cancer immunotherapy will be discussed.

AB - During tumor growth the extracellular matrix (ECM) undergoes dramatic remodeling. The normal ECM is degraded and substituted with a tumor-specific ECM, which is often of higher collagen density and increased stiffness. The structure and collagen density of the tumor-specific ECM has been associated with poor prognosis in several types of cancer. However, the reason for this association is still largely unknown. Collagen can promote cancer cell growth and migration, but recent studies have shown that collagens can also affect the function and phenotype of various types of tumor-infiltrating immune cells such as tumor-associated macrophages (TAMs) and T cells. This suggests that tumor-associated collagen could have important immune modulatory functions within the tumor microenvironment, affecting cancer progression as well as the efficacy of cancer immunotherapy. The effects of tumor-associated collagen on immune cells could help explain why a high collagen density in tumors is often correlated with a poor prognosis. Knowledge about immune modulatory functions of collagen could potentially identify targets for improving current cancer therapies or for development of new treatments. In this review, the current knowledge about the ability of collagen to influence T cell activity will be summarized. This includes direct interactions with T cells as well as induction of immune suppressive activity in other immune cells such as macrophages. Additionally, the potential effects of collagen on the efficacy of cancer immunotherapy will be discussed.

KW - cancer immunology

KW - collagen

KW - extracellular matrix

KW - immunotherapy

KW - macrophages

KW - matrix immunology

KW - T cells

KW - tumor microenvironment

U2 - 10.3389/fimmu.2021.791453

DO - 10.3389/fimmu.2021.791453

M3 - Review

C2 - 34956223

AN - SCOPUS:85121617993

VL - 12

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 791453

ER -