HLA and skin cancer

Bonamigo, Renan Rangel; Carvalho, André Vicente Esteves de; Sebastiani, Vanessa Raquel Zaleski; Silva, Cristina Martino da; Pinto, Angela Caroline de Zorzi

doi:10.1590/s0365-05962012000100001

Cited by 17 publications

(11 citation statements)

References 29 publications

(27 reference statements)

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“…Recent findings have suggested that antigenic repertoire variability is a crucial factor in tumor progression and immunosurveillance (Dunn et al, 2004). For instance, HLA-class I and II proteins have been shown to have a significant role in the progression of melanoma (Gogas et al, 2010;Bonamigo et al, 2012;Kandilarova et al, 2016). Thus, it is important to understand which specific HLA alleles from class-I and class-II could affect the survival of the patients.…”

Section: Discussionmentioning

confidence: 99%

“…The HLA complex is the highly polymorphic genetic region located on chromosome 6, precisely in the 6p21.3 region (Beck and Trowsdale, 2000;Choo, 2007). Major histocompatibility complex (MHC) encodes more than 200 immune-related genes, from which approximately 40 genes are associated with the development of leukocyte antigen, i.e., class I and class II HLA genes (Bonamigo et al, 2012). Class I and II regions are categorized into classical and non-classical, where, classical HLA-class I comprises of HLA-A, HLA-B, and HLA-C, and class II HLA gene loci are HLA-DR, HLA-DP, and HLA-DQ (Shiina et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Computing Skin Cutaneous Melanoma Outcome From the HLA-Alleles and Clinical Characteristics

et al. 2020

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Human leukocyte antigen (HLA) are essential components of the immune system that stimulate immune cells to provide protection and defense against cancer. Thousands of HLA alleles have been reported in the literature, but only a specific set of HLA alleles are present in an individual. The capability of the immune system to recognize cancer-associated mutations depends on the presence of a particular set of alleles, which elicit an immune response to fight against cancer. Therefore, the occurrence of specific HLA alleles affects the survival outcome of cancer patients. In the current study, prediction models were developed, using 401 cutaneous melanoma patients, to predict the overall survival (OS) of patients using their clinical data and HLA alleles. We observed that the presence of certain favorable superalleles like HLA-B * 55 (HR = 0.15, 95% CI 0.034-0.67), HLA-A * 01 (HR = 0.5, 95% CI 0.3-0.8), is responsible for the improved OS. In contrast, the presence of certain unfavorable superalleles such as HLA-B * 50 (HR = 2.76, 95% CI 1.284-5.941), HLA-DRB1 * 12 (HR = 3.44, 95% CI 1.64-7.2) is responsible for the poor survival. We developed prediction models using key 14 HLA superalleles, demographic, and clinical characteristics for predicting high-risk cutaneous melanoma patients and achieved HR = 4.52 (95% CI 3.088-6.609, p-value = 8.01E-15). Eventually, we also provide a web-based service to the community for predicting the risk status in cutaneous melanoma patients (https://webs.iiitd.edu.in/raghava/skcmhrp/).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Computing Skin Cutaneous Melanoma Outcome From the HLA-Alleles and Clinical Characteristics

et al. 2020

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“…Associations between aberrant human leukocyte antigen (HLA) expression (75,76), or germline class-I and II allelic variations and keratinocyte carcinoma have been controversial (77)(78)(79)(80) and are affected by high UV exposure (81), immunosuppression (82), and HPV infection (83). Multiple variants in HLA-DRB1 ( Ã 01, Ã 07) have shown increased risk for BCC while HLA-DRB1 Ã 04 was protective (82).…”

Section: Germline Genetic Risk Factors and Risk Modelsmentioning

confidence: 99%

Keratinocyte Carcinomas: Current Concepts and Future Research Priorities

Nagarajan

Asgari

Green

et al. 2019

Clinical Cancer Research

102

123

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Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are keratinocyte carcinomas, the most frequently diagnosed cancers in fair-skinned populations. Ultraviolet radiation (UVR) is the main driving carcinogen for these tumors, but immunosuppression, pigmentary factors, and aging are also risk factors. Scientific discoveries have improved the understanding of the role of human papillomaviruses (HPV) in cSCC as well as the skin microbiome and a compromised immune system in the development of both cSCC and BCC. Genomic analyses have uncovered genetic risk variants, high-risk susceptibility genes, and somatic events that underlie common pathways important in keratinocyte carcinoma tumorigenesis and tumor characteristics that have enabled development of prediction models for early identification of high-risk individuals. Advances in chemoprevention in high-risk individuals and progress in targeted and immune-based treatment approaches have the potential to decrease the morbidity and mortality associated with these tumors. As the incidence and prevalence of keratinocyte carcinoma continue to increase, strategies for prevention, including effective sun-protective behavior, educational interventions, and reduction of tanning bed access and usage, are essential. Gaps in our knowledge requiring additional research to reduce the high morbidity and costs associated with keratinocyte carcinoma include better understanding of factors leading to more aggressive tumors, the roles of microbiome and HPV infection, prediction of response to therapies including immune checkpoint blockade, and how to tailor both prevention and treatment to individual risk factors and needs.

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“…As a result, some cell-surface antigens are lost and others are expressed. At the end of this process, the tumour may no longer be recognized by the immune system [62]. Structural and functional changes in HLA, loss of expression of tumour antigens, lack of co-stimulatory molecules and production of immunosuppressive cytokines are some of the possible mechanisms that cause tumour cells to escape immune surveillance [63].…”

Section: Hla and Cancermentioning

confidence: 99%

Clinical Role of Human Leukocyte Antigen in Health and Disease

2015

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Most of the genes in the major histocompatibility complex (MHC) region express high polymorphism that is fundamental for their function. The most important function of human leukocyte antigen (HLA) molecule is in the induction, regulation of immune responses and the selection of the T cell repertoire. A clinician's attention is normally drawn to a system only when it malfunctions. The HLA system is no exception in this regard, but in contrast to other systems, it also arouses interest when it functions well -too well, in fact. Population studies carried out over the last several decades have identified a long list of human diseases that are significantly more common among individuals that carry particular HLA alleles including inflammatory, autoimmune and malignant disorders. HLAdisease association is the name of this phenomenon, and the mechanism underlying is still a subject of hot debate. Social behaviours are affected by HLA genes and preference for HLA disparate mates may provide 'good genes' for an individual's offspring. Also, certain HLA genes may be associated with shorter life and others with longer lifespan, but the effects depend both on the genetic background and on the environmental conditions. The following is a general overview of the important functional aspects of HLA in health and diseases.

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HLA and skin cancer

Cited by 17 publications

References 29 publications

Computing Skin Cutaneous Melanoma Outcome From the HLA-Alleles and Clinical Characteristics

Computing Skin Cutaneous Melanoma Outcome From the HLA-Alleles and Clinical Characteristics

Keratinocyte Carcinomas: Current Concepts and Future Research Priorities

Clinical Role of Human Leukocyte Antigen in Health and Disease

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