Association of DRB1 and DRBQ haplotype 04:01~03:01 with HPV positive head and neck squamous cell carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6054-6054
Author(s):  
Arun Khattri ◽  
Zhixiang Zuo ◽  
Y-H Carol Tan ◽  
Nishant Agrawal ◽  
Mark W. Lingen ◽  
...  
Keyword(s):  
African American ◽  
Head And Neck ◽  
Sexual Transmission ◽  
Hla Typing ◽  
P Value ◽  
Sequencing Data ◽  
Episomal Hpv16 ◽  
Hla Haplotypes ◽  
Tumor Types ◽  
Risk Of Cancer

6054 Background: The incidence of human papilloma virus (HPV) associated oropharyngeal head and neck cancer (HNC) is increasing rapidly in the US, Europe, and Asia. HPV16 is etiologic in 90-95% of HPV+ HNC. Sexual transmission and inability to clear infection leading to viral genome integration or chronic presence of episomal HPV16 DNA are precursors to HPV+ HNC carcinogenesis. However it remains unclear why a majority of HPV16 exposed individuals are able to clear the initial infection and avoid the risk of cancer. We hypothesized that difference in the ability eradicate infection may be mediated by certain HLA haplotypes. Methods: HPV(+) HNC patients from the TCGA cohort were HLA-typed based on available exome sequencing data. HLA typing was performed using the ATHLATES algorithm. We compared the distribution of alleles and haplotypes of classical HLA genes (A, C, B, DRB1 and DQB1) among HPV(+) HNC patients with those found in HPV(-) patients. Furthermore we evaluated enrichment of candidate alleles compared to publically available data in Caucasian non-cancer individuals. Results: Out of 528 HNC samples in the TCGA cohort, 450 were of Caucasian ancestry. The DRB1~DQB1 haplotype 04:01~03:01 was significantly increased in HPV(+) HNSCC patients compared to normal, non-cancer individuals ( p-value = 0.0045, OR = 2.52, 95% CI = 1.2–5.03). This was not the case for HPV(-) HNC patients. The number of African American samples in TCGA was comparably small (N = 48, with N = 5 being HPV+) however the frequency of DRB1~DQB1 haplotype 04:01~03:01 in the general African American population is significantly lower. Conclusions: DRB1~DQB1 haplotype 04:01~03:01 associates with an elevated risk for HPV+ HNC. Similar findings were reported 17 years ago for cervical cancer (Br J Cancer, 82(7), 1348–1352), and further validate our findings across tumor types. Mechanistic studies to understand potential DRB1~DQB1 haplotype 04:01~03:01 HPV specific immune dysfunction, as well as evaluation in different risk and racial populations are indicated.

Neoantigen-based vaccination as a practical measure for head and neck cancer treatment.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18528-e18528
Author(s):  
Xiao-bin Zheng ◽  
Chuan-ben Chen ◽  
Yu Chen ◽  
Shiguang Hao ◽  
Liu Jun ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Cancer Treatment ◽  
Head And Neck ◽  
Neck Cancer ◽  
Hla Typing ◽  
Sequencing Data ◽  
Coding Regions ◽  
Standard Procedures ◽  
Potential Vaccine ◽  
Practical Measure

e18528 Background: The view that neoantigens serve as potential vaccine targets has arisen in the last decade. Clinical and computational efforts have been done to increase the practicality of its application in real world. With these advances, we conducted a retrospective study on a Chinese population to explore the clinical feasibility of neoantigen-based vaccines for head and neck cancer treatment. Methods: Tumor and normal samples were profiled using a 1021-gene panel. Sequencing data were pre-analyzed according to our in-house standard procedures. Class I HLA typing was completed using OptiType v1.0. Curated somatic mutations in coding regions (SNVs and non-frameshift Indels with an allele frequency ≥ 5%) were collected and altered peptides produced by these mutations were analyzed using NetMHCpan v4.0. Peptides with an IC50 < 500 nM were considered potential binders, and especially, those with an IC50 < 50 nM were considered strong binders. An altered peptide was considered a neoantigen if IC50 altered is < IC50 wildtype. Results: We analyzed a total of 243 patients and detected 114 unique HLA alleles. By carrier percentage, the top three alleles are C*01:02 (44%), B*46:01 (36%), and A*11:01 (33%). In total, 743 mutations were deemed eligible for neoantigen prediction and 223 unique neoantigens were found. Of these neoantigens, 67 (carried by 21% of patients) were strong binders, among which 26 (carried by 9% patients) exhibited a great fold change (≥ 5 folds) of binding affinity. Moreover, the neoantigens in these patients are unique, as only two neoantigens were shared. A search for shared neoantigens revealed a combination of mutation PIK3CA p.E542K and HLA A*11:01, which was detected in 0.54% of all patients. Additionally, 43.6% (106/243) of patients were diagnosed with nasopharyngeal carcinoma, among whom 42% (44/106) possessed predicted neoantigens, including 15 patients with strong-binder neoantigens. Conclusions: (1) Neoantigen-based vaccination is a practical measure to treat patients with head and neck cancer, as indicated by the percentage of patients harboring strong-binder neoantigens. (2) Off-the-shelf neoantigen vaccines may not be practical, given the result that the most common combination of a neoantigen-producing mutation and the corresponding HLA was only found in 0.54% of all patients.

scholarly journals Human Leukocyte Antigen Matched Unrelated Donors for Patients with Sickle Cell Disease According to Geographic Origin: Results of International Donor Searches

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1021-1021 ◽  
Author(s):  
Karina Tozatto-Maio ◽  
Margareth Afonso Torres ◽  
Neifi Hassan Saloum Degaide ◽  
Juliana Fernandes Cardoso ◽  
Fernanda Volt ◽  
...  
Keyword(s):  
African American ◽  
Stem Cell ◽  
Ethnic Groups ◽  
Human Leukocyte ◽  
Haplotype Frequency ◽  
P Value ◽  
Unrelated Donor ◽  
International Donor ◽  
Hla Haplotypes ◽  
Brazilian Cohort

Background: Hematopoietic stem cell transplantation (HSCT), the only available curative therapy for sickle cell disease (SCD), remains hampered by the lack of histocompatible stem cell donors. Most patients will not have a suitable human leukocyte antigen(HLA) matched sibling donor. In addition, SCD affects ethnic groups that are underrepresented in stem cell donor registries worldwide. Objective: to assess the probability of having a potential allelic HLA matched unrelated donor(MUD) for HLA-A,B and DRB1 loci (6/6) in international donor registries for patients with SCD. Methods: 185 patients with SCD were included, 116 from Brazil, of whom 23 underwent HSCT, and 69 patients who underwent HSCT in centers reporting to the European Society for Blood and Marrow Transplantation (EBMT). All patients had HLA typing available at intermediate or high resolution. For intermediate resolution, using the National Marrow Donor Program (NMDP) code, we assigned alleles based on allele frequencies.We performed HLA haplotype estimation using the HaploStats website, which describes HLA haplotype frequency from the NMDP registry for the following ethnic groups: Caucasian, African-American, Asian, Hispanic and Native American. Because Hispanic is not a primary ethnicity, we did not consider this group in our analyses. Based on haplotype frequency of each ethnic group, we defined the most likely ethnicity for each estimated haplotype; those with frequency >1:1000 in all ethnic groups were named common. Unrelated donor search was done using the World Marrow Donor Association (WMDA) algorithm, which is based on haplotype matching. A potential allelic donor was defined as a full match high resolution 6/6 donor. Because it is described that testing at least 5 potential allelic donors simultaneously increases the chances of having a real donor, we assessed the probability of finding at least 1 and at least 5 potential allelic donors. Patients who received HSCT from MUD were excluded from donor searches (n=10).Comparisons of probabilities of having potential allelic donors between Brazilian and EBMT cohorts were performed by chi-square. Results: In the Brazilian cohort, from 181 HLA haplotypes, 45% were classified as African-American, 18% common, 12% Caucasian, 9% Amerindian and 16% could not be classified. In the EBMT cohort, from 116 HLA haplotypes, 70% were classified as African-American, 8% common, 6% Caucasian, 3% Amerindian and 13% were not classified. Although Brazilians showed greater genetic admixture, chances of finding at least one potential allelic MUD were 47% in both groups (p-value not significant) and chances of having at least 5 potential allelic MUD were 24% for Brazilians and 15% for EBMT (p-value not significant). Overall, most potential allelic MUD were found in the NMDP registry, followed by the Brazilian registry (REDOME) and by the German registry (ZKMD); for the Brazilian cohort, most potential allelic MUD were found in REDOME. Discussion: Migration from Africa to Brazil started at the colonial period, and interethnic admixture have been occurring since then, explaining the higher diversity observed in the Brazilian cohort. Despite differences in ethnic composition, chances of having at least one potential allelic MUD are identical, probably because carrying at least one African or Amerindian haplotype decreases the chances of a full HLA matching. Although we demonstrated higher probabilities of finding a potential allelic MUD in SCD than previous studies, the chances are still low, therefore further strategies are required to increase donor representativeness for SCD. In this setting, alternative sources, such as haploidentical HSCT and cord blood, should be considered. Also, our study might help to predict the probabilities of finding a MUD for patients with SCD. This is important because given that HSCT in SCD has better results if performed at earlier age, knowing which patients are less likely to find a MUD might influence therapy management. Disclosures No relevant conflicts of interest to declare.

scholarly journals Recombination within the HLA-D region. Correlation of molecular genotyping with functional data.

1984 ◽  
Vol 160 (1) ◽  
pp. 222-238 ◽  
Author(s):  
M A Robinson ◽  
E O Long ◽  
A H Johnson ◽  
R J Hartzman ◽  
B Mach ◽  
...  
Keyword(s):  
Functional Data ◽  
Southern Blot Analysis ◽  
Hla Typing ◽  
Subtle Difference ◽  
Molecular Genotyping ◽  
Recombinant Haplotype ◽  
Allelic Differences ◽  
D Region ◽  
The Individual ◽  
Hla Haplotypes

Molecular genotyping of the HLA-D/DR region in a family correlated with serologic and cellular typing data. It was further possible to predict a subtle difference in SB region-related functions from such molecular studies. A family that included an individual who inherited an HLA haplotype with a paternal recombination between HLA-B and the HLA-D/DR region was identified by classic HLA typing techniques. Segregation of HLA-D/DR region genes in this family was studied by Southern blot analysis using cDNA probes for DR alpha, DR beta, DC alpha, DC beta, and SB beta. Restriction enzyme fragment polymorphisms observed for every gene tested were in concordance with assigned HLA haplotypes (including the individual known to have inherited a paternal recombinant haplotype) with one exception: two HLA identical siblings were observed to have different SB beta restriction fragment patterns. Further testing revealed that one individual inherited a maternal HLA haplotype recombinant between the HLA-D/DR region and SB beta. Although both maternal SB alleles typed as SB4, allelic differences could be detected cellularly by primed lymphocytes and by the differential expression of a class II cell surface antigen using monoclonal antibody. Therefore, predicted and nonpredicted recombinant haplotypes were detected in a family by molecular genotyping.

P–530 The use of wide thresholds for detecting intermediate chromosomal CNV up to 80% doesn’t improve PGT-A ability to discriminate true mosaic from uniformly aneuploid embryos

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
L Girardi ◽  
M Serdaroğulları ◽  
C Patassini ◽  
S Caroselli ◽  
M Costa ◽  
...  
Keyword(s):  
Inner Cell Mass ◽  
False Negative ◽  
Cell Mass ◽  
Categorical Variables ◽  
P Value ◽  
Sequencing Data ◽  
Preimplantation Genetic Testing ◽  
Exact Test ◽  
Institutional Review ◽  
Wide Range

Abstract Study question What is the effect of varying diagnostic thresholds on the accuracy of Next Generation Sequencing (NGS)-based preimplantation genetic testing for aneuploidies (PGT-A)? Summary answer When single trophectoderm biopsies are tested, the employment of 80% upper threshold increases mosaic calls and false negative aneuploidy results compared to more stringent thresholds. What is known already Trophectoderm (TE) biopsy coupled with NGS-based PGT-A technologies are able to accurately predict Inner Cell Mass’ (ICM) constitution when uniform whole chromosome aneuploidies are considered. However, minor technical and biological inconsistencies in NGS procedures and biopsy specimens can result in subtle variability in analytical results. In this context, the stringency of thresholds employed for diagnostic calls can lead to incorrect classification of uniformly aneuploid embryos into the mosaic category, ultimately affecting PGT-A accuracy. In this study, we evaluated the diagnostic predictivity of different aneuploidy classification criteria by employing blinded analysis of chromosome copy number values (CNV) in multifocal blastocyst biopsies. Study design, size, duration The accuracy of different aneuploidy diagnostic cut-offs was assessed comparing chromosomal CNV in intra-blastocysts multifocal biopsies. Enrolled embryos were donated for research between June and September 2020. The Institutional Review Board at the Near East University approved the study (project: YDU/20l9/70–849). Embryos diagnosed with uniform chromosomal alterations (single or multiple) in their clinical TE biopsy (n = 27) were disaggregated into 5 portions: the ICM and 4 TE biopsies. Overall, 135 specimens were collected and analysed. Participants/materials, setting, methods Twenty-seven donated blastocysts were warmed and disaggregated in TE biopsies and ICM (n = 135 biopsies). PGT-A analysis was performed using Ion ReproSeq PGS kit and Ion S5 sequencer (ThermoFisher). Sequencing data were blindly analysed with Ion-Reporter software. Intra-blastocyst comparison of raw NGS data was performed employing different thresholds commonly used for aneuploidy classification. CNV for each chromosome were reported as aneuploid according to 70% or 80% thresholds. Categorical variables were compared using Fisher’s exact test. Main results and the role of chance In this study, a total of 50 aneuploid patterns in 27 disaggregated embryos were explored. Single TE biopsy results were considered as true positive when they displayed the same alteration detected in the ICM at levels above the 70% or 80% thresholds. Alternatively, alterations detected in the euploid or mosaic range were considered as false negative aneuploidy results. When the 70% threshold was applied, aneuploidy findings were confirmed in 94.5% of TE biopsies analyzed (n = 189/200; 95%CI=90.37–37.22), while 5.5% showed a mosaic profile (50–70%) but uniformly abnormal ICM. Positive (PPV) and negative predictive value (NPV) per chromosome were 100.0% (n = 189/189; 95%CI=98.07–100.00) and 99.5% (n = 2192/2203; 95%CI=99.11–99.75) respectively. When the upper cut-off was experimentally placed at 80% of abnormal cells, a significant decrease (p-value=0.0097) in the percentage of confirmed aneuploid calls was observed (86.5%; n = 173/200; 95%CI=80.97–90.91), resulting in mosaicism overcalling, especially in the high range (50–80%). Less stringent thresholds led to extremely high PPV (100.0%; n = 173/173; 95%CI=97.89–100.00), while NPV decreased to 98.8% (n = 2192/2219; 95%CI=98.30–99.23). Furthermore, no additional true mosaic patterns were identified with the use of wide range thresholds for aneuploidy classification. Limitations, reasons for caution This approach involved the analysis of aneuploidy CNV thresholds at the embryo level and lacked from genotyping-based confirmation analysis. Moreover, aneuploid embryos with known meiotic partial deletion/duplication were not included. Wider implications of the findings: The use of wide thresholds for detecting intermediate chromosomal CNV up to 80% doesn’t improve PGT-A ability to discriminate true mosaic from uniformly aneuploid embryos, lowering overall diagnostic accuracy. Hence, a proportion of the embryos diagnosed as mosaic using wide calling thresholds may actually be uniformly aneuploid and inadvertently transferred. Trial registration number N/A

Abstract P181: Cardiac Structure is Associated with Obesity and Blood Pressure But Not Inflammation

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Robert A Palermo ◽  
Samuel S Gidding ◽  
Stehpanie S DeLoach ◽  
Scott W Keith ◽  
Bonita Falkner
Keyword(s):  
Blood Pressure ◽  
African American ◽  
Left Ventricular Mass Index ◽  
African American Adolescents ◽  
Female Gender ◽  
Left Ventricular ◽  
P Value ◽  
Cardiac Structure ◽  
Z Score ◽  
Pai 1

Purpose: The aim of this study was to identify risk factors associated with cardiac structure in a cohort of African American adolescents oversampled for obesity and high blood pressure (BP). Additional associations of cardiac structure with a pro-inflammatory adipokine profile (low adiponectin, elevated IL6, PAI-1 and CRP) were sought. Methods: A cross-sectional study was conducted using a two-by-two factorial design with four groups of African American adolescents based on BP (prehypertension or stage 1 hypertension=high BP) and body mass index (BMI > 95% =obese) designation. Measurements included: echocardiogram, anthropomorphics, BP (on 3 separate occasions), high sensitivity CRP and plasma adipokines (adiponectin, IL6, PAI-1). Standardized echocardiogram measurements were used to obtain left ventricular mass index (LVMI, g/m 2.7 ) and left atrial diameter index (LADI, mm/m 2 ). Ordinary least-squares regression with model selection by Mallow's Cp was used to determine if pro-inflammatory adipokine profile predicted LV mass and LA diameter in models including age, gender, BMI z-score, and systolic BP. Results: Data on 251 African American adolescents, ages 13-19, were analyzed. BMI-z score was strongly associated with a pro-inflammatory adipokine profile whereas high BP was not. Variation in LADI was significantly associated with BMI (β=0.12, p<0.01) and female gender (β=0.08, p=0.04). LVMI variation was significantly associated with BMI (β=3.53, p<0.01), age (β=0.71, p<0.01), female gender (β=-4.32, p<0.01), and systolic BP (β=0.10, p=0.03). Though significant in univariate models, inflammatory markers were not significantly associated with LADI or LVMI after BMI adjustment. Conclusions: In African American adolescents, BMI is an important determinant of LADI and LVMI. Obesity is associated with a pro-inflammatory adipokine profile but LADI and LVMI are not. Table. Regression modeling results after variable selection by Mallow C p : Left Atrium Diameter Index and Left Ventricular Mass Index (N = 251) LADI LVMI Estimate (95% CL) p-value Estimate (95% CL) p-value Age (yr) 0.00063 (-0.021, 0.023) 0.955 0.71 ( 0.18, 1.24) 0.009 Gender (F) 0.08 ( 0.01, 0.16) 0.036 −4.32 (-6.13,-2.51) <.001 BMI z-score 0.12 ( 0.08, 0.16) <.001 3.53 ( 2.66, 4.40) <.001 Systolic BP 0.0019 (-0.0017, 0.0055) 0.306 0.0952 ( 0.0085, 0.1819) 0.032

scholarly journals Structural Analysis of Variability and Interaction of the N-terminal of the Oncogenic Effector CagA of Helicobacter pylori with Phosphatidylserine

2018 ◽  
Vol 19 (10) ◽  
pp. 3273 ◽  
Author(s):  
Cindy Ulloa-Guerrero ◽  
Maria Delgado ◽  
Carlos Jaramillo
Keyword(s):  
Crystal Structure ◽  
Helicobacter Pylori ◽  
Conservation Score ◽  
Intermolecular Forces ◽  
P Value ◽  
Cytotoxin Associated Gene A ◽  
Molecular Forces ◽  
Severe Pathology ◽  
Risk Of Cancer ◽  
Bulk Effect

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA’s translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the phosphatidylserine and the docking of three mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA–Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score; mutations in this position were evaluated to observe the differences in intermolecular forces for the CagA–Phosphatidylserine complex. We evaluated the docking of three mutations: K636A, K636R and K636N. The crystal and mutation models presented a ΔG of −8.919907, −8.665261, −8.701923, −8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the ΔG and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the ΔG ( χ 2 ( 1 ) = 93.82 , p-value < 2.2 × 10 − 16 ) and the H-bonds ( χ 2 ( 1 ) = 91.93 , p-value < 2.2 × 10 − 16 ). Overall, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA–Phosphatidylserine complex interaction.

scholarly journals Decomposing the subclonal structure of tumors with two-way mixture models on copy number aberrations

2018 ◽  
Author(s):  
An-Shun Tai ◽  
Chien-Hua Peng ◽  
Shih-Chi Peng ◽  
Wen-Ping Hsieh
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Copy Number ◽  
Tumor Heterogeneity ◽  
Tumor Evolution ◽  
Depth Information ◽  
Sequencing Data ◽  
Single Nucleotide Variants ◽  
Copy Number Aberrations

AbstractMultistage tumorigenesis is a dynamic process characterized by the accumulation of mutations. Thus, a tumor mass is composed of genetically divergent cell subclones. With the advancement of next-generation sequencing (NGS), mathematical models have been recently developed to decompose tumor subclonal architecture from a collective genome sequencing data. Most of the methods focused on single-nucleotide variants (SNVs). However, somatic copy number aberrations (CNAs) also play critical roles in carcinogenesis. Therefore, further modeling subclonal CNAs composition would hold the promise to improve the analysis of tumor heterogeneity and cancer evolution. To address this issue, we developed a two-way mixture Poisson model, named CloneDeMix for the deconvolution of read-depth information. It can infer the subclonal copy number, mutational cellular prevalence (MCP), subclone composition, and the order in which mutations occurred in the evolutionary hierarchy. The performance of CloneDeMix was systematically assessed in simulations. As a result, the accuracy of CNA inference was nearly 93% and the MCP was also accurately restored. Furthermore, we also demonstrated its applicability using head and neck cancer samples from TCGA. Our results inform about the extent of subclonal CNA diversity, and a group of candidate genes that probably initiate lymph node metastasis during tumor evolution was also discovered. Most importantly, these driver genes are located at 11q13.3 which is highly susceptible to copy number change in head and neck cancer genomes. This study successfully estimates subclonal CNAs and exhibit the evolutionary relationships of mutation events. By doing so, we can track tumor heterogeneity and identify crucial mutations during evolution process. Hence, it facilitates not only understanding the cancer development but finding potential therapeutic targets. Briefly, this framework has implications for improved modeling of tumor evolution and the importance of inclusion of subclonal CNAs.

scholarly journals Transcriptomic Correlates of Immunologic Activation in Head and Neck and Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Cristina Saiz-Ladera ◽  
Mariona Baliu-Piqué ◽  
Francisco J. Cimas ◽  
Aránzazu Manzano ◽  
Vanesa García-Barberán ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Immune System ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Effector ◽  
Effector Cells ◽  
Favorable Prognosis ◽  
Immune Effector Cells ◽  
Tumor Types

Targeting the immune system has emerged as an effective therapeutic strategy for the treatment of various tumor types, including Head and Neck Squamous Cell Carcinoma (HNSCC) and Non-small-Cell Lung Cancer (NSCLC), and checkpoint inhibitors have shown to improve patient survival in these tumor types. Unfortunately, not all cancers respond to these agents, making it necessary to identify responsive tumors. Several biomarkers of response have been described and clinically tested. As of yet what seems to be clear is that a pre-activation state of the immune system is necessary for these agents to be efficient. In this study, using established transcriptomic signatures, we identified a group of gene combination associated with favorable outcome in HNSCC linked to a higher presence of immune effector cells. CD2, CD3D, CD3E, and CXCR6 combined gene expression is associated with improved outcome of HNSCC patients and an increase of infiltrating immune effector cells. This new signature also identifies a subset of cervical squamous cell carcinoma (CSCC) patients with favorable prognosis, who show an increased presence of immune effector cells in the tumor, which outcome shows similarities with the HP-positive HNSCC cohort of patients. In addition, CD2, CD3D, CD3E, and CXCR6 signature is able to predict the best favorable prognosis in terms of overall survival of CSSC patients. Of note, these findings were not reproduced in other squamous cell carcinomas like esophageal SCC or lung SCC. Prospective confirmatory studies should be employed to validate these findings.

scholarly journals HLA allele-specific expression loss in tumors can shorten survival and hinder immunotherapy

2020 ◽  
Author(s):  
Ioan Filip ◽  
Rose Orenbuch ◽  
Junfei Zhao ◽  
Gulam Manji ◽  
Evangelina López de Maturana ◽  
...  
Keyword(s):  
Overall Survival ◽  
Human Leukocyte ◽  
Prognostic Indicator ◽  
Cancer Prognosis ◽  
Sequencing Data ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific ◽  
Tumor Types ◽  
Expression Loss

AbstractEfficient presentation of aberrant peptide fragments by the human leukocyte antigen class I (HLA-I) genes is necessary for immune detection and killing of cancer cells. Patient HLA-I genotypes are known to impact the efficacy of cancer immunotherapy, and the somatic loss of HLA-I heterozygosity has been established as a factor in immune evasion. While global deregulated expression of HLA-I has been reported in different tumor types, the role of HLA-I allele-specific expression loss – that is, the preferential RNA expression loss of specific HLA-I alleles – has not been fully characterized in cancer. In the present study, we quantified HLA-I allele-specific expression (ASE) across eleven TCGA tumor types using a novel method from input RNA and whole-exome sequencing data. Allele-specific loss in at least one of the three HLA-I genes (ASE loss) was pervasive and associated to worse overall survival across tumor types, including pancreatic adenocarcinomas, prostate carcinomas and glioblastomas, among others. In particular, our analysis shows that detection of neoantigens with binding affinity to the specific HLA-I genes subject to ASE loss was a top prognostic indicator of overall survival. Additionally, we found that ASE loss hindered immunotherapy in retrospective analyses. Together, these results highlight the prevalence of HLA-I ASE loss – a previously uncharacterized phenomenon in cancer – and provide initial evidence of its clinical significance in cancer prognosis and immunotherapy treatment.

scholarly journals ROLE OF ACCESS OSTEOTOMY IN HEAD AND NECK LESIONS – A REVIEW

2021 ◽  
pp. 25-30
Author(s):  
BHARATHI K ◽  
MANOJ CHANDRASEKAR ◽  
KAPIL DEV KUMAR S ◽  
BALA JAGANNATH GUPTA B
Keyword(s):  
Head And Neck ◽  
Surgical Resection ◽  
Hand Search ◽  
Surgical Access ◽  
Operative Care ◽  
Specific Tumor ◽  
Surgical Field ◽  
Tumor Types ◽  
Neurovascular Structures

The surgical resection of the head and neck lesions summarizes the principles, classifications, applications, complications, and post-operative care of osteotomy with the standard protocols performed safely. It often poses a great surgical challenge due to the anatomical complexity, difficulty in accessibility, and proximity of vital structures. A multidisciplinary approach is often required in these situations for their better exposure to provide surgical access. Access osteotomy is the choice and type for these head and neck lesions, which are most often based on the anatomic extent of the lesion, vascularity of the lesion, and involvement of neurovascular structures in and around it. The literature search using Medline from the year 1986 to 2019 were performed and textbooks were also collected by hand search from the same period. The role of aggressive surgical resection has not been established for malignant head and neck lesions with the technical feasibility and its efficacy for specific tumor types must be defined by the future studies. Thus, we would like to conclude that access osteotomy allows the surgeon a better view and an access of the surgical field to resect the tumor completely with safer margins, preserving the vital structures, pre-operative functions, and reducing post-operative complications.

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