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Is HLA type a possible cancer risk modifier in Lynch syndrome?

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Editorial Material Gastroenterology & Hepatology

Broadening our Understanding of the Immune Landscape in Lynch Syndrome

Sonia S. Kupfer

GASTROENTEROLOGY (2022)

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HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study

Vivek Naranbhai et al.

Summary: This study aimed to determine the effect of HLA-A*03 as a biomarker for predicting response to immunotherapy. The results showed that the HLA-A*03 gene was associated with reduced overall survival after immunotherapy and this effect was observed across different types of immunotherapy agents and tumor types.

LANCET ONCOLOGY (2022)

Article Cell Biology

Polymorphism of the HLA system and weak antibody response to BNT162b2 mRNA vaccine

Roberto Crocchiolo et al.

Summary: The HLA system polymorphism has been extensively studied in COVID-19 infection, but there is no data about its role in vaccine response. This study found that certain HLA alleles and haplotypes, along with age, are associated with a weaker antibody response after the BNT162b2 mRNA vaccine. These findings provide insights into tracking potentially susceptible individuals, but further research is needed to confirm and dissect the role of HLA polymorphism in response to anti-COVID-19 vaccines.
Article Gastroenterology & Hepatology

The Different Immune Profiles of Normal Colonic Mucosa in Cancer-Free Lynch Syndrome Carriers and Lynch Syndrome Colorectal Cancer Patients

Lena Bohaumilitzky et al.

Summary: The immune infiltrate in tumor-distant normal colorectal mucosa from individuals with Lynch syndrome (LS) was assessed. It was found that LS carriers show elevated mucosal T-cell infiltration even in the absence of cancer, and this immune profile may impact tumor risk in LS carriers.

GASTROENTEROLOGY (2022)

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PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer

Andrea Cercek et al.

Summary: This study found that mismatch repair-deficient, locally advanced rectal cancer is highly sensitive to PD-1 blockade. Additionally, no adverse events of grade 3 or higher have been reported, and no cases of progression or recurrence have been observed. Longer follow-up is needed to assess the duration of response.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Spontaneous regression of mismatch repair-deficient colorectal cancers: Case series

Takahiro Utsumi et al.

Summary: Spontaneous regression in colorectal cancer is rare and often associated with specific endoscopic characteristics, lack of DNA mismatch repair proteins, and a deficiency in mismatch repair (dMMR). The activation of anti-tumor host immune responses through increased tumor-infiltrating lymphocytes may play a role in the spontaneous regression of colorectal cancer.

DIGESTIVE ENDOSCOPY (2021)

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European guidelines from theEHTGandESCPfor Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender

T. T. Seppala et al.

Summary: Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed clinical guidance focusing on surgical and gastroenterological aspects of the cancer spectrum.

BRITISH JOURNAL OF SURGERY (2021)

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Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity With Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model

Johannes Gebert et al.

Summary: The study identified 4 shared FSP neoantigens that induced CD4/CD8 T cell responses in naive C57BL/6 mice. Vaccination with a combination of 4 FSPs significantly increased FSP-specific adaptive immunity, reduced intestinal tumor burden, and prolonged overall survival in VCMsh2 mice. Combining FSP vaccination with daily naproxen treatment potentiated immune response, delayed tumor growth, and prolonged survival more effectively than FSP vaccination alone.

GASTROENTEROLOGY (2021)

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HLA Zygosity Increases Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma

Zhiwei Liu et al.

Summary: The study found that an increase in the number of homozygous HLA class II loci is associated with an increased risk of chronic HBV infection and HBV-associated HCC. Specifically, HLA-DQB1 homozygosity is significantly associated with HCC risk.

JOURNAL OF INFECTIOUS DISEASES (2021)

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The influence of HLA genotype on the severity of COVID-19 infection

David J. Langton et al.

Summary: The impact of COVID-19 varies significantly among individuals and populations. This study found that differences in HLA genes may influence the clinical outcome of COVID-19 infection. Specifically, the presence of specific HLA genes, such as DRB1*04:01, was associated with the severity of COVID-19 symptoms.
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Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study

Mark A. Jenkins

Summary: The study identified significant familial risk factors affecting colorectal cancer risk for Lynch syndrome carriers, resulting in a wide variation in risk between carriers of the same gene. This highlights the importance of personalized risk assessments for precision prevention and early detection of colorectal cancer in individuals with Lynch syndrome.

LANCET ONCOLOGY (2021)

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Precision Treatment and Prevention of Colorectal Cancer-Hope or Hype?

Charles Muller et al.

GASTROENTEROLOGY (2020)

Review Medicine, General & Internal

Implications of Hereditary Origin on the Immune Phenotype of Mismatch Repair-Deficient Cancers: Systematic Literature Review

Lena Bohaumilitzky et al.

JOURNAL OF CLINICAL MEDICINE (2020)

Article Oncology

Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer

Alicia Latham et al.

JOURNAL OF CLINICAL ONCOLOGY (2019)

Review Pathology

HLA testing in the molecular diagnostic laboratory

Kathleen Madden et al.

VIRCHOWS ARCHIV (2019)

Review Genetics & Heredity

A genomic perspective on HLA evolution

Diogo Meyer et al.

IMMUNOGENETICS (2018)

Review Urology & Nephrology

HLA in transplantation

Robert A. Montgomery et al.

NATURE REVIEWS NEPHROLOGY (2018)

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Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

Aida Ferreiro-Iglesias et al.

NATURE COMMUNICATIONS (2018)

Article Oncology

Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer

Aung Ko Win et al.

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION (2017)

Article Multidisciplinary Sciences

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

Dung T. Le et al.

SCIENCE (2017)

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Classification and characterization of microsatellite instability across 18 cancer types

Ronald J. Hanse et al.

NATURE MEDICINE (2016)

Review Oncology

The Immune Biology of Microsatellite-Unstable Cancer

Matthias Kloor et al.

TRENDS IN CANCER (2016)

Article Medicine, General & Internal

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

D. T. Le et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

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Towards a vaccine to prevent cancer in Lynch syndrome patients

Magnus von Knebel Doeberitz et al.

FAMILIAL CANCER (2013)

Article Oncology

Genome-wide Association Study of Susceptibility Loci for Cervical Cancer

Dan Chen et al.

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2013)

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Postreplicative Mismatch Repair

Josef Jiricny

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY (2013)

Article Oncology

Candidate driver genes in microsatellite-unstable colorectal cancer

Pia Alhopuro et al.

INTERNATIONAL JOURNAL OF CANCER (2012)

Article Biochemical Research Methods

Accurate HLA type inference using a weighted similarity graph

Minzhu Xie et al.

BMC BIOINFORMATICS (2010)

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Hereditary and Familial Colon Cancer

Kory W. Jasperson et al.

GASTROENTEROLOGY (2010)

Review Cell Biology

A short history of HLA

E. Thorsby

TISSUE ANTIGENS (2009)

Article Gastroenterology & Hepatology

Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers

Yvette Schwitalle et al.

GASTROENTEROLOGY (2008)

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Human leukocyte antigen and its role in transplantation biology

V. B. Trivedi et al.

TRANSPLANTATION PROCEEDINGS (2007)

Review Oncology

Systematic review of microsatellite instability and colorectal cancer prognosis

S Popat et al.

JOURNAL OF CLINICAL ONCOLOGY (2005)

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Frameshift peptide-derived T-cell epitopes: a source of novel tumor-specific antigens

M Linnebacher et al.

INTERNATIONAL JOURNAL OF CANCER (2001)

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Evolution of instability at coding and non-coding repeat sequences in human MSI-H colorectal cancers

A Duval et al.

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J Klein et al.

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J Klein et al.

NEW ENGLAND JOURNAL OF MEDICINE (2000)