Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment.

ELife
A. Nicolas-BoludaEmmanuel Donnadieu

Abstract

Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing five preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tumor stiffening with the remodeling of ECM architecture and to determine how these features affect intratumoral T cell migration. An ECM-targeted strategy, based on the inhibition of lysyl oxidase, was used. In vivo stiffness measurements were found to be strongly correlated with tumor growth and ECM crosslinking but negatively correlated with T cell migration. Interfering with collagen stabilization reduces ECM content and tumor stiffness leading to improved T cell migration and increased efficacy of anti-PD-1 blockade. This study highlights the rationale of mechanical characterizations in solid tumors to understand resistance to immunotherapy and of combining treatment strategies targeting the ECM with anti-PD-1 therapy.

References

Jan 1, 1996·Annual Review of Physical Chemistry·R Richards-Kortum, E Sevick-Muraca
Sep 1, 2005·Clinical & Experimental Metastasis·Alexander D BorowskyJeffrey P Gregg
May 22, 2008·AJR. American Journal of Roentgenology·Sudhakar K VenkateshRichard L Ehman
Nov 26, 2009·Cell·Kandice R LeventalValerie M Weaver
Sep 9, 2010·Current Opinion in Cell Biology·Mikala EgebladValerie M Weaver
Nov 1, 2011·European Biophysics Journal : EBJ·Katarzyna PogodaMałgorzata Lekka
Feb 2, 2012·The Journal of Clinical Investigation·Hélène SalmonEmmanuel Donnadieu
Oct 23, 2012·Nature Nanotechnology·Marija PlodinecCora-Ann Schoenenberger
May 8, 2013·Cellular and Molecular Life Sciences : CMLS·Elisa PeranzoniEmmanuel Donnadieu
Oct 31, 2014·Nature Reviews. Molecular Cell Biology·Jay D HumphreyMartin A Schwartz
Nov 10, 2014·EMBO Reports·Michael W PickupValerie M Weaver
Apr 4, 2015·Science·Johanna A Joyce, Douglas T Fearon
Apr 11, 2015·Cancer Cell·Jacques F A P Miller, Michel Sadelain
Oct 17, 2015·Nature Reviews. Immunology·Shannon J TurleyJillian L Astarita
Jan 7, 2016·Cancer Research·Thomas R CoxJanine T Erler
Apr 15, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ila Datar, Kurt A Schalper
Apr 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Priti S HegdeStefan Evers
May 19, 2016·Immunity·Margaret K CallahanJedd D Wolchok
Dec 31, 2016·Proceedings of the National Academy of Sciences of the United States of America·Francois BordeleauCynthia A Reinhart-King
Apr 28, 2017·Nature Communications·Julienne L CarstensRaghu Kalluri
Apr 30, 2017·Cancer Immunology, Immunotherapy : CII·Hong JiangDavid G DeNardo
Jan 3, 2018·The Journal of Clinical Investigation·Mitsuo YamauchiJonathan M Kurie
Jan 5, 2018·Science Translational Medicine·Marsha C Lampi, Cynthia A Reinhart-King
Jan 11, 2018·Nature·Zeynep ErogluAntoni Ribas
Feb 15, 2018·Nature·Daniele V F TaurielloEduard Batlle

❮ Previous
Next ❯

Citations

Oct 24, 2021·Cancer Immunology Research·Chahrazade Kantari-MimounEmmanuel Donnadieu

❮ Previous
Next ❯

Software Mentioned

MATLAB
Image J
GraphPad Prism
CT
Imaris
FIRE

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.