HLA Class II Antigen Expression in Colorectal Carcinoma Tumors as a Favorable Prognostic Marker

Sconocchia, Giuseppe; Eppenberger‐Castori, Serenella; Zlobec, Inti; Karamitopoulou, Evanthia; Arriga, Roberto; Coppola, Andrea; Caratelli, Sara; Spagnoli, Giulio C.; Lauro, Davide; Lugli, Alessandro; Han, Jiazhen; Iezzi, Giovanna; Ferrone, Cristina R.; Ferlosio, Amedeo; Tornillo, Luigi; Droeser, Raoul A.; Rossi, Piero; Attanasio, Aldo; Terracciano, Luigi

doi:10.1593/neo.131568

Cited by 96 publications

(93 citation statements)

References 52 publications

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“…78,79 In addition, even within defined cancer types, the prognostic value of HLA class II antigens is conflicting depending on the studies. Immunohistochemically detectable HLA class II antigen expression was associated with a better prognostic outcome of CRC patients in some studies, 36 but not associated with tumor grade, stage and survival in other studies. 37,80 A positive prognostic effect of HLA class II antigen expression in CRC may reflect the increased T-cell infiltration which is one of the strongest favorable prognostic biomarkers in CRC.…”

Section: Deregulation Of Hla Class II Apm Components In Malignant Cellsmentioning

confidence: 83%

“…For example, the frequency of HLA class II positivity in colorectal carcinoma (CRC) reported in the literature varied between 21 and 55% depending on the study. [34][35][36][37][38] These different results may reflect differences in the methodology and antibodies used, in the characteristics of the patients' population included in the studies and in the molecular pathogenesis of the disease. In this context, it is noteworthy that HLA class II antigen expression in CRC is closely related to the high-level microsatellite instability (MSI-H) phenotype 33,39 underlining that a precise molecular classification is required to obtain reliable information about the frequency of HLA class II antigen expression in defined tumor subtypes.…”

Section: Expression Of Hla Class II Antigens In Malignant Tumorsmentioning

confidence: 99%

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HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

2017

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The human leukocyte antigen (HLA) class II antigen-processing machinery (APM) presents to cognate CD4 C T-cells antigenic peptides mainly generated from exogeneous proteins in the endocytic compartment. These CD4 C T cells exert helper function, but may also act as effector cells, thereby recognizing HLA class II antigen-expressing tumor cells. Thus, HLA class II antigen expression by tumor cells influences the tumor antigen (TA)-specific immune responses and, depending on the cancer type, the clinical course of the disease. Many types of human cancers express HLA class II antigens, although with marked differences in their frequency. Some types of cancer lack HLA class II antigen expression, which could be due to structural defects or deregulation affecting different components of the complex HLA class II APM and/or from lack of cytokine(s) in the tumor microenvironment. In this review, we have summarized the information about HLA class II antigen distribution in normal tissues, the structural organization of the HLA class II APM, their expression and regulation in malignant cells, the defects, which have been identified in malignant cells, and their functional and clinical relevance.

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Section: Deregulation Of Hla Class II Apm Components In Malignant Cellsmentioning

confidence: 83%

Section: Expression Of Hla Class II Antigens In Malignant Tumorsmentioning

confidence: 99%

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

2017

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“…LAG-3 binds to MHC Class II, a molecule shown to be expressed on CRC cells. 25 Given that blockade of LAG-3 increases T cell cytokine production and proliferation, 26 it may be possible that the higher expression of this molecule influences both the cytokine phenotype and limited proliferative capacity of the T cells as described here. T cells expressing PD-1 are susceptible to negative regulation by tumors (as well as Tregs) via PD-L1 -a molecule expressed on CRC tumors.…”

Section: Discussionmentioning

confidence: 94%

Functional impairment of infiltrating T cells in human colorectal cancer

et al. 2016

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T cells play a crucial role in preventing the growth and spread of colorectal cancer (CRC). However, immunotherapies against CRC have only shown limited success, which may be due to lack of understanding about the effect of the local tumor microenvironment (TME) on T cell function. The goal of this study was to determine whether T cells in tumor tissue were functionally impaired compared to T cells in non-tumor bowel (NTB) tissue from the same patients. We showed that T cell populations are affected differently by the TME. In the tumor, T cells produced more IL-17 and less IL-2 per cell than their counterparts from NTB tissue. T cells from tumor tissue also had impaired proliferative ability compared to T cells in NTB tissue. This impairment was not related to the frequency of IL-2 producing T cells or regulatory T cells, but T cells from the TME had a higher co-expression of inhibitory receptors than T cells from NTB. Overall, our data indicate that T cells in tumor tissue are functionally altered by the CRC TME, which is likely due to cell intrinsic factors. The TME is therefore an important consideration in predicting the effect of immune modulatory therapies.

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“…Growing evidence indicates that the expression of HLA class II antigens on CRC cells [6][7][8][9] is involved in the pathogenesis of CRC tumors, while DRB1 alleles influence the susceptibility to develop CRC tumors in colonic tissues with IBDs. [13][14][15] This information has provided the rationale to investigate the role of DRB1 alleles on the susceptibility to develop CRC tumors in patients with no history of IBDs.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5] Importantly, HLA class II antigen expression in solid tumor cells has been associated with favorable and unfavorable prognosis of CRC patients. [6][7][8][9] The reason(s) why that happens is (are) uncertain. 8 HLA class II antigen polymorphisms have been also implicated in conferring genetic susceptibility to immune-mediated diseases and tumors.…”

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HLA‐DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma

Aureli

Canossi

Beato

et al. 2014

Intl Journal of Cancer

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Increasing evidence suggests that HLA-DRB1 alleles reduce or increase the risk of developing ulcerative colitis-associated colorectal carcinoma (CRC) tumors. However, the role of HLA-DRB1 locus on the susceptibility to develop CRC tumor, in the absence of a history of inflammatory bowel diseases (IBDs), is unclear. The aim of our study was to determine whether HLA-DRB1 alleles are associated with IBD-independent CRC tumor. HLA-DRB1 allele polymorphisms were identified by sequence-based typing method in 53 CRC patients and 57 sex-and age-matched healthy Caucasian controls. Pearson's chisquared analysis with Yate's correction or Fisher's exact test with Bonferroni's correction, as appropriate, were used to compare the allele frequency (AF) differences of HLA-DRB1 in patients and controls. A total of 29 HLA-DRB1 alleles were recognized. A detailed study of these alleles allowed to identify DRB1*13:01 and DRB1*11:01 alleles that were significantly associated with an increased and reduced risk to develop CRC tumor, respectively. AF of DRB1*13:01, in CRC patients, was significantly higher than that of healthy controls, even following Bonferroni's correction (p 5 0.029). In contrast, the presence of the DRB1*11:01 allele was negatively associated with CRC tumor as evidenced by the significantly lower AF in CRC patients than that of healthy controls (p 5 0.005). However, following Bonferroni's correction, the AF of DRB*11:01 lost its statistical significance. These results suggest that HLA-DRB1*13:01 allele could be a potential marker for predicting genetic susceptibility to CRC tumor. In contrast, the protective role of DRB1*11:01 remains unclear.HLA-class II antigens (HLA-DR, DQ and DP) are key players of the immune response. They present extracellular antigen peptides to CD41 T cells.1 HLA class II antigens are expressed on the cell surface of immune cells such as B lymphocytes, activated CD41T cells, antigen-presenting cells including Langerhans and dendritic cells, macrophages and vascular endothelial cells, but not on connective and epithelial cells. 3-5 Importantly, HLA class II antigen expression in solid tumor cells has been associated with favorable and unfavorable prognosis of CRC patients.6-9 The reason(s) why that happens is (are) uncertain.8 HLA class II antigen polymorphisms have been also implicated in conferring genetic susceptibility to immune-mediated diseases and tumors.For example, the presence of HLA class II alleles DRB3*02/03 (DR52), DRB1*13 and DRB1*03 (DR17) was associated with an increased risk to develop cervical cancer, while DRB1*09:01:02 and DRB5*01/02 (DR51) were protective alleles.10 Lin et al. showed that DRB1*07 and DRB1*12 are associated with an increased risk to develop hepatocellular carcinoma.11 Conversely, Chaudhuri et al. found that HLA DQB1*03:03:02 and DRB1*11 alleles are instead associated with a reduced risk of breast cancer.12 Garrity-Park et al. showed that the presence of particular HLA-DRB1 alleles may also reduce or increase the risk of developing

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HLA Class II Antigen Expression in Colorectal Carcinoma Tumors as a Favorable Prognostic Marker

Cited by 96 publications

References 52 publications

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

Functional impairment of infiltrating T cells in human colorectal cancer

HLA‐DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma

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