Insights Into Unveiling a Potential Role of Tertiary Lymphoid Structures in Metastasis

TY - JOUR

T1 - Insights Into Unveiling a Potential Role of Tertiary Lymphoid Structures in Metastasis

AU - Mustapha, Rami

AU - Ng, Kenrick

AU - Monypenny, James

AU - Ng, Tony

N1 - Funding Information: This work was supported by the CRUK City of London Centre (C7893/A26233), CRUK KHP Centre and CRUK National Cancer Imaging Translational Accelerator (C604/A25135 and C1519/28,682, support of RM), and CRUK Clinical Research Training Fellowships (Award Number 549580, support of KN). Publisher Copyright: © Copyright © 2021 Mustapha, Ng, Monypenny and Ng.

PY - 2021/9/8

Y1 - 2021/9/8

N2 - Tertiary lymphoid structures (TLSs) develop in non-lymphatic tissue in chronic inflammation and cancer. TLS can mature to lymph node (LN) like structures with germinal centers and associated vasculature. TLS neogenesis in cancer is highly varied and tissue dependent. The role of TLS in adaptive antitumor immunity is of great interest. However, data also show that TLS can play a role in cancer metastasis. The importance of lymphatics in cancer distant metastasis is clear yet the precise detail of how various immunosurveillance mechanisms interplay within TLS and/or draining LN is still under investigation. As part of the tumor lymphatics, TLS vasculature can provide alternative routes for the establishment of the pre-metastatic niche and cancer dissemination. The nature of the cytokine and chemokine signature at the heart of TLS induction can be key in determining the success of antitumor immunity or in promoting cancer invasiveness. Understanding the biochemical and biomechanical factors underlying TLS formation and the resulting impact on the primary tumor will be key in deciphering cancer metastasis and in the development of the next generation of cancer immunotherapeutics.

AB - Tertiary lymphoid structures (TLSs) develop in non-lymphatic tissue in chronic inflammation and cancer. TLS can mature to lymph node (LN) like structures with germinal centers and associated vasculature. TLS neogenesis in cancer is highly varied and tissue dependent. The role of TLS in adaptive antitumor immunity is of great interest. However, data also show that TLS can play a role in cancer metastasis. The importance of lymphatics in cancer distant metastasis is clear yet the precise detail of how various immunosurveillance mechanisms interplay within TLS and/or draining LN is still under investigation. As part of the tumor lymphatics, TLS vasculature can provide alternative routes for the establishment of the pre-metastatic niche and cancer dissemination. The nature of the cytokine and chemokine signature at the heart of TLS induction can be key in determining the success of antitumor immunity or in promoting cancer invasiveness. Understanding the biochemical and biomechanical factors underlying TLS formation and the resulting impact on the primary tumor will be key in deciphering cancer metastasis and in the development of the next generation of cancer immunotherapeutics.

KW - high endothelial venule (HEV)

KW - interstitial fluid pressure

KW - lymphangiogeneis

KW - metastasis

KW - premetastatic niche

KW - tertiary lymphoid organs

KW - tissue stress

KW - TLS

UR - http://www.scopus.com/inward/record.url?scp=85115438872&partnerID=8YFLogxK

U2 - 10.3389/fmolb.2021.661516

DO - 10.3389/fmolb.2021.661516

M3 - Article

AN - SCOPUS:85115438872

SN - 2296-889X

VL - 8

JO - Frontiers in Molecular Biosciences

JF - Frontiers in Molecular Biosciences

M1 - 661516

ER -