CD103+ CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17

Cell Reports Medicine
Stéphanie CorgnacFathia Mami-Chouaib

Abstract

Accumulation of CD103+CD8+ resident memory T (TRM) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of TRM to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multiplex immunofluorescence on cohorts of non-small cell lung cancer patients treated with anti-PD-(L)1, we show that an increased density of CD103+CD8+ lymphocytes in immunotherapy-naive tumors is associated with greatly improved outcomes. The density of CD103+CD8+ cells increases during immunotherapy in most responder, but not in non-responder, patients. CD103+CD8+ cells co-express CD49a and CD69 and display a molecular profile characterized by the expression of PD-1 and CD39. CD103+CD8+ tumor TRM, but not CD103-CD8+ tumor-infiltrating counterparts, express Aiolos, phosphorylated STAT-3, and IL-17; demonstrate enhanced proliferation and cytotoxicity toward autologous cancer cells; and frequently display oligoclonal expansion of TCR-β clonotypes. These results explain why CD103+CD8+ TRM are associated with better outcomes in anti-PD-(L)1-treated patients.

References

Apr 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Nadia AnikeevaYuri Sykulev
Sep 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tonia WoodberryChristian Brander
Jul 30, 2009·Cancer Research·Katarzyna FranciszkiewiczFathia Mami-Chouaib
Dec 17, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kensuke TakadaStephen C Jameson
Sep 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Maike Hofmann, Hanspeter Pircher
Mar 30, 2012·Omics : a Journal of Integrative Biology·Guangchuang YuQing-Yu He
Apr 18, 2012·Proceedings of the National Academy of Sciences of the United States of America·Laura K MackayThomas Gebhardt
Jul 4, 2012·Nature Immunology·Francisco J QuintanaVijay K Kuchroo
Nov 6, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John R WebbBrad H Nelson
Mar 29, 2014·The Journal of Clinical Investigation·Alena GrosSteven A Rosenberg
Jan 28, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura K MackayThomas Gebhardt
Mar 1, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fayçal DjenidiFathia Mami-Chouaib
Apr 30, 2015·Nature Methods·Dmitriy A BolotinDmitriy M Chudakov
Nov 1, 2016·Nature Immunology·Pleun HombrinkRené A W van Lier
Nov 9, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maria ParkhurstSteven A Rosenberg
Mar 7, 2017·Nature Methods·Rob PatroCarl Kingsford
May 26, 2017·Nature Communications·Mevyn NizardEric Tartour
Jun 6, 2017·Nature Methods·Harold PimentelLior Pachter
Jun 20, 2017·Nature Immunology·Anusha-Preethi GanesanChristian H Ottensmeier
Dec 7, 2017·Nature·J Justin MilnerAnanda W Goldrath
Feb 17, 2018·The Journal of Experimental Medicine·Tianxia GuanSusan M Kaech
Mar 31, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jarem EdwardsUmaimainthan Palendira
Jul 15, 2018·Nature Communications·Thomas DuhenAndrew D Weinberg
Aug 30, 2018·The Journal of Experimental Medicine·Jolanda BrummelmanEnrico Lugli

❮ Previous
Next ❯

Datasets Mentioned

BETA
EGAS00001004707

Methods Mentioned

BETA
flow cytometry
PMA
ELISA
confocal microscopy
RNA-seq
RNAseq

Software Mentioned

MiXCR
Ventana Benchmark
Gencode
MiXCR package
ImmunoSEQ Analyzer
InForm
wasabi
R
Ingenuity Pathway Analysis
GSEA

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.