The use of HLA class I tetramers to design a vaccination strategy for melanoma patients

2002 ◽  
Vol 188 (1) ◽  
pp. 155-163 ◽  
Author(s):  
Michael Palmowski ◽  
Mariolina Salio ◽  
Rod P. Dunbar ◽  
Vincenzo Cerundolo
2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8029-8029
Author(s):  
H. Gogas ◽  
M. Spyropoulou-Vlachou ◽  
U. Dafni ◽  
D. Tsoutsos ◽  
C. Markopoulos ◽  
...  

8029 Background: Serological typing for both HLA class I and class II antigen expression, has previously shown association of specific HLA antigen expression with clinical response and survival in patients with metastatic melanoma treated with IL-2 (e.g. HLA-DQ1). Purpose: To evaluate the impact of HLA class I (low-resolution) and class II (high-resolution) expression, on the outcome of high-risk melanoma patients receiving adjuvant high-dose interferon. Methods: 181 stage IIB, IIC and III melanoma patients (88 female and 93 male), median age 52.1 years and 246 healthy controls were included in this study. DNA was used for the determination of HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1 genotypes. Results: With a median follow-up of 37 months, 59 (group 1) patients have remained with no evidence of recurrence and 122 have recurred (group 2). Statistical significant differences between the two groups, were found in the following genotypes: HLA-A*02 (42% vs. 57.3%, p=0.08), HLA-A*33 (15.2% vs. 6.5%, p=0.05), HLA-B*51 (15.2% vs. 34.4%, p=0.01), HLA-B*57 (11.8% vs. 2.4%, p=0.02). Statistical significant differences between group 1 and healthy controls, were found in the following genotypes: HLA-A*33 (15.2% vs. 6.5%, p=0.05), HLA-B*51 (15.2% vs. 28.5%, p=0.05), HLA-B*57 (11.8% vs. 4.5%, p=0.05), HLA-Cw*03 (23.7% vs. 11%, p=0.01), HLA-Cw*06 (27.1% vs. 16.1%, p=0.06), HLA-DRB1*0701 (27.1% vs. 13.4%, p=0.01), HLA-DRB1*1601 (35.6% vs. 22.3%, p=0.01), HLA-DQB1*0202 (23.8% vs. 10.1%, p=0.09). Conclusions: Statistical significant differences were seen in HLA-A and HLA-B alleles between the patients with high-risk melanoma free of recurrence and those who recurred after treatment with adjuvant interferon. Additionally, differences were seen between healthy controls and melanoma patients free of recurrence. No significant financial relationships to disclose.


1998 ◽  
Vol 16 (4) ◽  
pp. 1430-1437 ◽  
Author(s):  
D S Hoon ◽  
T Okamoto ◽  
H J Wang ◽  
R Elashoff ◽  
A J Nizze ◽  
...  

PURPOSE An allogeneic polyvalent melanoma cell vaccine (PMCV) has been shown to be efficacious in improving overall survival of patients with malignant melanoma in a phase II clinical setting. The PMCV consists of three allogeneic melanoma cell lines. The objectives of the study were to determine (1) whether the survival of melanoma patients who received PMCV was related to the patient's human leukocyte antigen (HLA) class I phenotype matching the HLA class I phenotype of the PMCV, and (2) whether PMCV clinical efficacy was correlated to melanoma patients with a particular HLA phenotype(s). MATERIALS AND METHODS PMCV was given to 69 melanoma patients with American Joint Committee on Cancer (AJCC) stage I to IV disease status. The PMCV and patients lymphocytes were typed for HLA-A and -B. A correlation was made between the HLA expression of PMCV lines and the HLA of patients to their survival status. A second correlation was made between the HLA of patients and survival independent of the PMCV HLA phenotype. RESULTS Patients whose HLA phenotype (A3/11 and B7/44) matched the PMCV lines had a better overall survival (P < .029). Analysis of HLA expression of patients independent of PMCV HLA to survival showed that HLA-A25 phenotype patients had a significantly better overall survival (P = .006). HLA-B35 patients had a poorer survival outcome (P = .019). CONCLUSION The studies indicate that overall survival following PMCV treatment in melanoma patients significantly correlates with their HLA phenotypes. These correlations may be related to the host immune response to the PMCV or due to differences in the clinical course of melanoma in patients with different HLA types.


2001 ◽  
Vol 57 (6) ◽  
pp. 508-519 ◽  
Author(s):  
R. Mendez ◽  
A. Serrano ◽  
E. Jäger ◽  
I. Maleno ◽  
F. Ruiz-Cabello ◽  
...  

2020 ◽  
Author(s):  
Shouxiong Huang ◽  
Ming Tan

AbstractMemory CD8+ T cells are associated with a better outcome in Coronavirus Disease 2019 (COVID-19) and recognized as promising vaccine targets against viral infections. This study determined the efficacy of population-dominant and infection-relevant human leukocyte antigens (HLA) class I proteins to present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides through calculating binding affinities and simulating CD8+ T cell responses. As a result, HLA class I proteins distinguished or shared various viral peptides derived from viruses. HLA class I supertypes clustered viral peptides through recognizing anchor and preferred residues. SARS-CoV-2 peptides overlapped significantly with SARS but minimally with common human coronaviruses. Immune simulation of CD8+ T cell activation using predicted SARS-CoV-2 peptide antigens depended on high-affinity peptide binding, anchor residue interaction, and synergistic presentation of HLA class I proteins in individuals. Results demonstrated that multi-epitope vaccination, employing a strong binding affinity, viral adjuvants, and heterozygous HLA class I genes, induced potent immune responses. Therefore, optimal CD8+ T cell responses can be achieved and customized contingent on HLA class I genotypes in human populations, supporting a precise vaccination strategy to combat COVID-19.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Xu Wang ◽  
Francisco Almazan ◽  
Yoel Genaro Montoyo-Pujol ◽  
Antonia Martin-Casares ◽  
Aurelio Martin ◽  
...  

Background. The influence of HLA class I and II loci on the susceptibility to melanoma remains an area of intense debate. This study aimed to examine whether the HLA system was related to melanoma susceptibility and prognosis in a southern Spanish population. Methods. In this study, HLA class I and class II genotyping were performed using polymerase chain reaction sequence-specific oligonucleotides (PCR-SSO) in 237 Spanish melanoma patients and 636 ethnically matched controls. Data were analyzed according to the clinical characteristics of the defined subgroups. Results. Compared to the control group, DRB1 ∗ 16:01 (4% vs. 1.3%, p = 0.001 , Pc = 0.035, OR = 3.28) and DQB1 ∗ 05:02 (4.9% vs. 2%, p = 0.001 , Pc = 0.017, OR = 2.54) were positivity associated with the susceptibility to melanoma. Both DRB1 ∗ 16:01 (5.4% vs. 1.3%, p = 0.001 , Pc = 0.035, OR = 4.46) and DQB1 ∗ 05:02 (6.5% vs. 2%, p = 0.001 , Pc = 0.017, OR = 3.44) also showed a positive correlation with Breslow thickness >1.5 mm, most notably at an early age of diagnosis (≤58 years), DRB1 ∗ 16:01 (4.2% vs. 1.3%, p = 0.001 , Pc = 0.035, OR = 3.41) and DQB1 ∗ 05:02 (5.4% vs. 2%, p = 0.002 , Pc = 0.034, OR = 2.86). Conclusion. These findings established HLA-DRB1 ∗ 16:01 and HLA-DQB1 ∗ 05:02 loci as melanoma risk factors in the southern Spanish population.


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