Acquisition of resistance to vemurafenib leads to interleukin-10 production through an aberrant activation of Akt in a melanoma cell line

The Journal of Dermatology
Takashi InozumeTatsuyoshi Kawamura

Abstract

Serine/threonine-protein kinase B-Raf (BRAF) inhibitors are very effective in treating melanoma with BRAF mutations. BRAF inhibitors suppress aberrant growth of melanoma cells caused by BRAF mutations. BRAF mutations reportedly result in melanoma cells releasing immunosuppressive factors, and BRAF inhibitors elicit anti-melanoma immune responses by reducing such factors. However, immunological characteristics of tumor cells that acquire resistance to BRAF inhibitors remain unknown. Here, we compared immunological characteristics between a melanoma cell line and its vemurafenib-resistant subline. No differences were observed in the status of BRAF mutations, expression of surface molecules related to antitumor T-cell responses or recognition by human leukocyte antigen-A*0201-matched melanoma-specific cytotoxic T lymphocytes in a short-term co-culture assay. However, resistant tumor cells released high amounts of interleukin-10 depending on aberrant activation of Akt signaling, and dendritic cell functions were considerably suppressed by culture supernatants of the resistant cells. Our findings demonstrated a novel immunological mechanism contributing to tumor growth owing to drug resistance to BRAF inhibitors.

References

Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Jul 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael MartinSuzanne M Michalek
Nov 3, 2005·Molecular Immunology·Ruma A PengalSusheela Tridandapani
Jun 28, 2006·The Journal of Experimental Medicine·Hidetoshi SumimotoYutaka Kawakami
Feb 24, 2012·The New England Journal of Medicine·Jeffrey A SosmanAntoni Ribas
Jul 21, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomonori YaguchiYutaka Kawakami
Aug 2, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jahan S KhaliliGregory Lizée
Jan 12, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dennie T FrederickJennifer A Wargo
Mar 5, 2013·The Journal of Clinical Investigation·Deborah A KnightMark J Smyth
Sep 17, 2014·Expert Review of Clinical Immunology·Marco TucciFranco Silvestris
Nov 18, 2014·The New England Journal of Medicine·Caroline RobertDirk Schadendorf
Oct 13, 2015·The Journal of Investigative Dermatology·Takashi InozumeShinji Shimada
Jan 15, 2016·The Journal of Investigative Dermatology·Takashi InozumeShinji Shimada
Jul 18, 2017·Journal of the American Academy of Dermatology·Virginia O VolpeJane M Grant-Kels
Mar 17, 2018·Journal of Hematology & Oncology·Julian A Marin-AcevedoYanyan Lou

❮ Previous
Next ❯

Citations

Jan 21, 2021·Biomedicines·Claudio TabolacciFrancesco Facchiano

❮ Previous
Next ❯

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.