Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells

Autor: Stephen B. Baylin, Anup Sharma, Rajita Vatapalli, Nita Ahuja, Katherine Kb Chiappinelli, Jana Jeschke, Angela A. Guzzetta, Cornelia Siebenkäs
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Cancer Treatment
lcsh:Medicine
Antigen Processing and Recognition
Ovarian Neoplasms -- genetics -- immunology -- metabolism -- pathology
Biochemistry
Testicular Neoplasms -- genetics -- immunology -- metabolism -- pathology
Major Histocompatibility Complex
Mice
0302 clinical medicine
Medicine and Health Sciences
lcsh:Science
Ovarian Neoplasms
Innate Immune System
Antigen Presentation
Multidisciplinary
DNA methylation
Antigen processing
DNA
Neoplasm
Sciences bio-médicales et agricoles
Chromatin
3. Good health
Ovarian Cancer
Nucleic acids
Oncology
DNA
Neoplasm -- genetics -- immunology -- metabolism
030220 oncology & carcinogenesis
Colonic Neoplasms
Cancer/testis antigens
Colonic Neoplasms -- genetics -- immunology -- metabolism -- pathology
Female
Epigenetics
Anatomy
DNA modification
Epigenetic therapy
Chromatin modification
Research Article
Chromosome biology
Antigen Presentation -- genetics
Cell biology
Colon
Antigen presentation
Immunology
Biology
03 medical and health sciences
Antigen
Testicular Neoplasms
Antigens
Neoplasm
medicine
Genetics
Animals
Humans
Colorectal Cancer
Biology and life sciences
lcsh:R
Correction
Cancers and Neoplasms
DNA
medicine.disease
Gastrointestinal Tract
DNA Methylation -- genetics -- immunology
030104 developmental biology
Antigens
Neoplasm -- biosynthesis -- genetics -- immunology
Immune System
Cancer cell
lcsh:Q
Clinical Immunology
Gene expression
Caco-2 Cells
Clinical Medicine
Ovarian cancer
Digestive System
Gynecological Tumors
Zdroj: PLoS ONE
PloS one, 12 (6
PLoS ONE, Vol 12, Iss 6, p e0179501 (2017)
ISSN: 1932-6203
Popis: Innovative therapies for solid tumors are urgently needed. Recently, therapies that harness the host immune system to fight cancer cells have successfully treated a subset of patients with solid tumors. These responses have been strong and durable but observed in subsets of patients. Work from our group and others has shown that epigenetic therapy, specifically inhibiting the silencing DNA methylation mark, activates immune signaling in tumor cells and can sensitize to immune therapy in murine models. Here we show that colon and ovarian cancer cell lines exhibit lower expression of transcripts involved in antigen processing and presentation to immune cells compared to normal tissues. In addition, treatment with clinically relevant low doses of DNMT inhibitors (that remove DNA methylation) increases expression of both antigen processing and presentation and Cancer Testis Antigens in these cell lines. We confirm that treatment with DNMT inhibitors upregulates expression of the antigen processing and presentation molecules B2M, CALR, CD58, PSMB8, PSMB9 at the RNA and protein level in a wider range of colon and ovarian cancer cell lines and treatment time points than had been described previously. In addition, we show that DNMTi treatment upregulates many Cancer Testis Antigens common to both colon and ovarian cancer. This increase of both antigens and antigen presentation by epigenetic therapy may be one mechanism to sensitize patients to immune therapies.
info:eu-repo/semantics/published
Databáze: OpenAIRE
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