Tumor MHC Expression Guides First-Line Immunotherapy Selection in Melanoma

Cancers
Elena ShklovskayaHelen Rizos

Abstract

Immunotherapy targeting T-cell inhibitory receptors, namely programmed cell death-1 (PD-1) and/or cytotoxic T-lymphocyte associated protein-4 (CTLA-4), leads to durable responses in a proportion of patients with advanced metastatic melanoma. Combination immunotherapy results in higher rates of response compared to anti-PD-1 monotherapy, at the expense of higher toxicity. Currently, there are no robust molecular biomarkers for the selection of first-line immunotherapy. We used flow cytometry to profile pretreatment tumor biopsies from 36 melanoma patients treated with anti-PD-1 or combination (anti-PD-1 plus anti-CTLA-4) immunotherapy. A novel quantitative score was developed to determine the tumor cell expression of antigen-presenting MHC class I (MHC-I) molecules, and to correlate expression data with treatment response. Melanoma MHC-I expression was intact in all tumors derived from patients who demonstrated durable response to anti-PD-1 monotherapy. In contrast, melanoma MHC-I expression was low in 67% of tumors derived from patients with durable response to combination immunotherapy. Compared to MHC-I high tumors, MHC-I low tumors displayed reduced T-cell infiltration and a myeloid cell-enriched microenvironment. Our data e...Continue Reading

References

Nov 26, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jedd D WolchokF Stephen Hodi
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Jun 2, 2015·The New England Journal of Medicine·James LarkinJedd D Wolchok
Feb 4, 2016·Immunology and Cell Biology·Elena ShklovskayaBarbara Fazekas de St. Groth
Aug 16, 2016·The Journal of Clinical Investigation·Adil I DaudMichael D Rosenblum
Nov 20, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Adil I DaudOmid Hamid
Dec 3, 2016·The Journal of Experimental Medicine·Antoni Ribas, Siwen Hu-Lieskovan
Apr 12, 2017·Nature·Alexander C HuangE John Wherry
Sep 12, 2017·The New England Journal of Medicine·Jedd D WolchokJames Larkin
Oct 27, 2017·Nature Communications·Moshe Sade-FeldmanNir Hacohen
Jul 7, 2018·Frontiers in Immunology·Sara AlaviHelen Rizos
Jul 20, 2018·Science Translational Medicine·Scott J RodigF Stephen Hodi
Aug 11, 2018·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Matteo S CarlinoAdil Daud
Aug 23, 2018·The New England Journal of Medicine·Hussein A TawbiKim Margolin
Nov 25, 2018·Journal for Immunotherapy of Cancer·Vivek VermaCharles R Thomas
Jun 5, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anu SharmaPadmanee Sharma
Sep 29, 2019·The New England Journal of Medicine·James LarkinJedd D Wolchok

❮ Previous
Next ❯

Citations

Mar 22, 2021·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R V RawsonR A Scolyer
May 14, 2021·Expert Opinion on Biological Therapy·Parmida Sadat PezeshkiNima Rezaei
Jul 3, 2021·International Journal of Molecular Sciences·Elena Shklovskaya, Helen Rizos

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
biopsies
biopsy
flow

Software Mentioned

GraphPad Prism
FlowJo

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.