&lt;p&gt;Major histocompatibility complex class II molecule in non-small cell lung cancer diagnosis, prognosis and treatment&lt;/p&gt;

Wang, Hao; Zhao, Sha; Zhang, Xiaoshen; Jia, Keyi; Deng, Juan; Zhou, Caicun; He, Yayi

doi:10.2147/ott.s214231

Cited by 12 publications

(12 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, HLA class-II proteins could contribute to NK-cell activation through interaction with the NKp44 receptor (34,38,39). Expression of HLA class-II proteins is constitutively found in multiple NSCLC cell lines and has been reported in 18%-30.2% of NSCLCs (29,(40)(41)(42). Our results using QIF showed comparable HLA class-II subunit expression levels in cancer and stromal cells in approximately 80% of samples from three independent cohorts, indicating that HLA class-II expression is a common event in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer

Datar

Hauc

Desai

et al. 2021

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: To analyze the distribution, associated immune contexture, and clinical significance of human leukocyte antigen (HLA) class-I and HLA class-II subunits in non–small cell lung cancer (NSCLC). Experimental Design: Using spatially resolved and quantitative multiplexed immunofluorescence we studied the tumor/stromal tissue distribution, cancer cell–specific defects, and clinicopathologic/survival associations of β2 microglobulin (β2M), HLA-A, and HLA-B,-C heavy chains, as well as HLA class-II β chain in >700 immunotherapy-naïve NSCLCs from four independent cohorts. Genomic analysis of HLA genes in NSCLC was performed using two publicly available cohorts. Results: Cancer cell–specific downregulation of HLA markers was identified in 30.4% of cases. β2M was downregulated in 9.8% (70/714), HLA-A in 9% (65/722), HLA-B,-C in 12.1% (87/719), and HLA class-II in 17.7% (127/717) of evaluable samples. Concurrent downregulation of β2M, HLA-B,-C, and HLA class-II was commonly identified. Deleterious mutations in HLA genes were detected in <5% of lung malignancies. Tumors with cancer cell–specific β2M downregulation displayed reduced T cells and increased natural killer (NK)–cell infiltration. Samples with cancer cell HLA-A downregulation displayed modest increase in CD8+ T cells and NK-cell infiltration. Samples with cancer cell–selective HLA-B,-C or HLA class-II downregulation displayed reduced T cells and NK-cell infiltration. There was limited association of the markers with clinicopathologic variables and KRAS/EGFR mutations. Cancer cell–selective downregulation of the HLA subunits was associated with shorter overall survival. Conclusions: Our results reveal frequent and differential defects in HLA class-I and HLA class-II protein subunit expression in immunotherapy-naïve NSCLCs associated with distinct tumor microenvironment composition and patient survival.

show abstract

Section: Discussionmentioning

confidence: 99%

Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer

Datar

Hauc

Desai

et al. 2021

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…The HLA-DOB*01:02 allele has also been associated with an increased risk of death in patients with non-small cell lung cancer; reduced median survival time ( 67 , 68 ), with type 1 diabetes ( 69 ), which is a major comorbidity related to severe Covid-19 ( 39 ), and with resistance to SARs-CoV-2 infection ( 22 ). DOB*01:02 has a different signal peptide, which may influence cellular localization and trafficking of the protein ( 15 ), possibly leading to inadequate antigen presentation.…”

Section: Discussionmentioning

confidence: 99%

MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil

et al. 2022

View full text Add to dashboard Cite

BackgroundAlthough aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome.MethodsSARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started.ResultsWe found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins’ family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24).ConclusionSince the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.

show abstract

“…The frequencies of MHC-II alleles in cancer patients are different from these observed in healthy subjects. These differences, which depend on the type of cancer, were found to correlate with the risk of developing the malignancy and with the response to treatment ( 66 ). It is tempting to believe that CD+4 T cells (and MHC-II expression) are important for anti-tumor immunity.…”

Section: Cancermentioning

confidence: 99%

Cancer and Autoimmune Diseases: A Tale of Two Immunological Opposites?

Elkoshi

2022

Front. Immunol.

View full text Add to dashboard Cite

The present article compares, side-by-side, cancer and autoimmune diseases in terms of innate and adaptive immune cells involvement, MHC Class I and Class II expression, TGFβ effect, immune modulating drugs effect and the effect of reactive oxygen species. The change in the inflammatory immune reaction during the progress of cancer and the effect of this change on the comorbidity of autoimmune diseases and cancer are discussed. The similar inflammatory properties of autoimmune diseases and early cancer, and the contrasting inflammatory properties of autoimmune diseases and advanced cancer elucidate the increased incidence of many types of cancer in patients with pre-existing autoimmune diseases and the decreased cancer-specific mortality of these patients. Stage-dependent effects of reactive oxygen-species on tumor proliferation are an additional probable cause for these epidemiological observations. The relationship: {standardized incidence ratio (SIR)} > {cancer-specific hazard ratio (HR)} for cancer patients with a history of autoimmune diseases is substantiated and rationalized.

show abstract

<p>Major histocompatibility complex class II molecule in non-small cell lung cancer diagnosis, prognosis and treatment</p>

Cited by 12 publications

References 65 publications

Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer

Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer

MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil

Cancer and Autoimmune Diseases: A Tale of Two Immunological Opposites?

Contact Info

Product

Resources

About