Monocyte-derived APCs are central to the response of PD1 checkpoint blockade and provide a therapeutic target for combination therapy.

Journal for Immunotherapy of Cancer
Sjoerd T T SchettersYvette Van Kooyk

Abstract

PD1 immune checkpoint blockade (αPD1 ICB) has shown unparalleled success in treating many types of cancer. However, response to treatment does not always lead to tumor rejection. While αPD1 ICB relies on cytotoxic CD8+ T cells, antigen-presenting cells (APCs) at the tumor site are also needed for costimulation of tumor-infiltrating lymphocytes (TILs). It is still unclear how these APCs develop and function before and during αPD1 ICB or how they are associated with tumor rejection. Here, we used B16 mouse melanoma and MC38 colorectal carcinoma tumor models, which show differential responses to αPD1 ICB. The immune composition of ICB insensitive B16 and sensitive MC38 were extensively investigated using multi-parameter flow cytometry and unsupervised clustering and trajectory analyses. We additionally analyzed existing single cell RNA sequencing data of the myeloid compartment of patients with melanoma undergoing αPD1 ICB. Lastly, we investigated the effect of CD40 agonistic antibody on the tumor-infiltrating monocyte-derived cells during αPD1 ICB. We show that monocyte-derived dendritic cells (moDCs) express high levels of costimulatory molecules and are correlated with effector TILs in the tumor microenvironment (TME) after αPD...Continue Reading

References

Nov 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fernando O MartinezAlberto Mantovani
Feb 6, 2010·Science·Frederic GeissmannKlaus Ley
Jun 5, 2012·The New England Journal of Medicine·Suzanne L TopalianMario Sznol
Aug 30, 2013·Science Translational Medicine·Stefani SprangerThomas F Gajewski
Jan 28, 2015·Cancer Immunology Research·Alfred ZippeliusPhilipp Müller
Mar 31, 2015·Nature Methods·Aaron M NewmanAsh A Alizadeh
Apr 11, 2015·Cancer Cell·Suzanne L TopalianDrew M Pardoll
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Dec 17, 2015·Bioinformatics·Philipp AngererFlorian Buettner
Jul 21, 2016·Journal for Immunotherapy of Cancer·Marc SchwartzJoseph D Rosenblatt
Nov 4, 2016·Nature Reviews. Cancer·Laurence ZitvogelGuido Kroemer
Dec 8, 2016·Cancer Immunology Research·Suzanne I S MoselyRobert W Wilkinson
Jan 24, 2017·Cell·Matthew H SpitzerEdgar G Engleman
Jan 24, 2017·Nature Methods·Xiaojie QiuCole Trapnell
Feb 12, 2017·Cell·Padmanee SharmaAntoni Ribas
Feb 14, 2017·Current Opinion in Immunology·Filippo Veglia, Dmitry I Gabrilovich
Nov 18, 2017·Nucleic Acids Research·Antonio FabregatPeter D'Eustachio
Jan 9, 2018·Nature Medicine·Carsten KriegBurkhard Becher
Mar 14, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kimio YonesakaKazuhiko Nakagawa
Mar 24, 2018·Science·Antoni Ribas, Jedd D Wolchok
Apr 11, 2018·Cancer Cell·Robert H Vonderheide
Apr 13, 2018·Science Translational Medicine·Natalie J NeubertDaniel E Speiser
Apr 17, 2018·The New England Journal of Medicine·Matthew D HellmannLuis Paz-Ares

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE91061

Methods Mentioned

BETA
FACS
Flow
flow cytometry
RNA-seq
biopsies

Software Mentioned

CITRUS of SAM
R
GSVA
FlowJo
Reactome analysis
R package destiny
flowCore
TSNE
R package Rtsne
SPADE

Related Concepts

Related Feeds

Cancer Immunotherapy

Cancer immunotherapy is an important field of research that is looking at controlling cancer and tumor growth by activating the individuals own immune system. Recent studies have utilized chimeric antigen receptor t-cell therapy, immune checkpoint inhibitors and neoantigen vaccines. Discover the latest research on cancer immunotherapy here.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.