HLA Class I Allele Expression and Clinical Outcome in De Novo Metastatic Prostate Cancer

Stokidis, Savvas; Fortis, Sotirios P.; Kogionou, Paraskevi; Anagnostou, Τ.; Perez, Sonia A.; Baxevanis, Constantin N.

doi:10.3390/cancers12061623

Cited by 7 publications

(18 citation statements)

References 45 publications

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“…The resulting repertoire is for example defined by foreign antigens from encountered viruses. In a small European cohort with de novo metastatic prostate cancer ( n = 56), HLA‐A*02:01 and HLA‐A*24:02 have been suggested to have prognostic implications [ 4 ], but beyond that, little is known about the role of HLA‐type and antiviral immunity in prostate cancer. Human cytomegalovirus (CMV), a common herpes virus, is a master modulator of the immune system [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity

et al. 2022

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Prostate cancer is a heterogeneous disease with a need for new prognostic biomarkers. Human leukocyte antigen (HLA) genes are highly polymorphic genes central to antigen presentation to T‐cells. Two alleles, HLA‐A*02:01 and HLA‐A*24:02, have been associated with prognosis in patients diagnosed with de novo metastatic prostate cancer. We leveraged the next‐generation sequenced cohorts CPC‐GENE and TCGA‐PRAD to examine HLA alleles, antiviral T‐cell receptors and prostate cancer disease recurrence after prostatectomy. Carrying HLA‐A*02:01 (111/229; 48% of patients) was independently associated with disease recurrence in patients with low‐intermediate risk prostate cancer. HLA‐A*11 (carried by 42/441; 10% of patients) was independently associated with rapid disease recurrence in patients with high‐risk prostate cancer. Moreover, HLA‐A*02:01 carriers in which anti‐cytomegalovirus T‐cell receptors (CMV‐TCR) were identified in tumors (13/144; 10% of all patients in the cohort) had a higher risk of disease recurrence than CMV‐TCR‐negative patients. These findings suggest that HLA‐type and CMV immunity may be valuable biomarkers for prostate cancer progression.

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Section: Introductionmentioning

confidence: 99%

Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity

et al. 2022

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“…Compared to HLA-B44 generally, specific HLA-B alleles that bring about radical glutamic acid substitutions in the anchor position of B44 were associated with a poor prognosis and better clinical outcomes with ICIs in NSCLC (11). Specific HLA-A alleles (A*02:01 and A*24:02) were also associated with the prognosis of metastatic hormone-sensitive prostate cancer (8). Studies on the implications of the HLA genotype in the immunotherapy response in other solid tumor types are also increasing (12,39).…”

Section: Ngs Typically Generates Short Read Lengths (Betweenmentioning

confidence: 92%

“…Alterations in the human leukocyte antigen (HLA) are implicated in tumor invasion and development via the promotion of T lymphocyte-mediated immune escape mechanisms (6). Recent research has shown that specific alterations in HLA class I loci are associated with the clinical outcomes of ICIs (7)(8)(9)(10)(11)(12), which increases the importance of accurate high-resolution HLA genotyping in immunooncology applications. The HLA gene complex encodes the major histocompatibility complex (MHC), which plays a major role in adaptive immunity by presenting pathogenderived peptides to T lymphocytes (13,14).…”

Section: Introductionmentioning

confidence: 99%

Benchmarking of 5 algorithms for high-resolution genotyping of human leukocyte antigen class I genes from blood and tissue samples

Hua¹,

Sun²,

Zhao³

et al. 2022

Ann Transl Med

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Background: Specific alterations in human leukocyte antigen class I (HLA-I) loci are associated with clinical outcomes for immune checkpoint inhibitors, which increase the clinical relevance of accurate highresolution HLA genotyping in immuno-oncology applications. Numerous algorithms have been developedfor high-to full-resolution HLA genotyping by next-generation sequencing (NGS) data; however, Sanger sequencing-based typing (SBT) remains the gold standard. With the increasing use of NGS for clinical oncology, it is important to identify the computational tool with comparable performance as the gold standard. This study aimed to benchmark 5 algorithms against SBT for the high-resolution typing of classical HLA-I genes for targeted NGS data from blood and tissue samples.Methods: Paired white blood cell (WBC), plasma, and tissue deoxyribonucleic acid (DNA) samples derived from 22 cancer patients with known HLA genotypes were sequenced using a panel of all the following exons of classical HLA-I genes: HLA-A, HLA-B, and HLA-C. NGS-based genotypes were generated by the 5 different algorithms, including HLA-HD, HLAscan, OptiType, Polysolver, and xHLA. Accuracy was defined as the concordance between the SBT and NGS-based algorithms. Accuracy was computed as the fraction of all the alleles with concordant genotype using the SBT and any of the algorithm over the total number of alleles. Results:In relation to the WBC, plasma, and tissue samples, all 5 algorithms were highly accurate at low-resolution HLA-I genotyping, but had more varied accuracy at high-resolution HLA-I genotyping, particularly in HLA-A. The in-silico analyses revealed that high-resolution genotyping by all 5 algorithms achieved approximately 90% accuracy at sequencing depths of 6,000× -100× for the WBC samples, at 6,000× -700× for the plasma samples, and at 1,000× -100× for the tissue samples. Among the 5 algorithms, HLA-HD was consistently accurate at high-resolution HLA-I genotyping, and had an accuracy of 93.9% for the WBC samples, 87.9% for the plasma samples, and 94.2% for tissue samples even at a 50× sequencing depth. Conclusions:We found that HLA-HD was an accurate algorithm for the high-resolution genotyping of classical HLA-I genes sequenced by our targeted panel, particularly at a sequencing depth ≥300× for blood and tissue samples.

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“…Antigen presenting MHCI molecules are highly polymorphic, especially at their peptide binding grooves, and therefore each allele can bind and present a restricted set of antigenic epitopes. As result/Consequently, individuals homozygous in at least one MHCI locus may present a smaller, less diverse repertoire of tumor antigens to CD8+ T cells and thus may be less likely to present potent epitopes that induce highly effective antitumor responses that can be enhanced by ICI therapy [ 135 , 136 ]. Given that only a small percentage of presented tumor antigens in cancer patients are immunogenic, it seems that even small differences in MHCI molecules can significantly affect the adaptive responses and the efficacy of immunotherapy.…”

Section: Mhci Expression In Cancersmentioning

confidence: 99%

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

Mpakali

Stratikos

2021

Cancers

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Recent clinical successes of cancer immunotherapy using immune checkpoint inhibitors (ICIs) are rapidly changing the landscape of cancer treatment. Regardless of initial impressive clinical results though, the therapeutic benefit of ICIs appears to be limited to a subset of patients and tumor types. Recent analyses have revealed that the potency of ICI therapies depends on the efficient presentation of tumor-specific antigens by cancer cells and professional antigen presenting cells. Here, we review current knowledge on the role of antigen presentation in cancer. We focus on intracellular antigen processing and presentation by Major Histocompatibility class I (MHCI) molecules and how it can affect cancer immune evasion. Finally, we discuss the pharmacological tractability of manipulating intracellular antigen processing as a complementary approach to enhance tumor immunogenicity and the effectiveness of ICI immunotherapy.

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HLA Class I Allele Expression and Clinical Outcome in De Novo Metastatic Prostate Cancer

Cited by 7 publications

References 45 publications

Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity

Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity

Benchmarking of 5 algorithms for high-resolution genotyping of human leukocyte antigen class I genes from blood and tissue samples

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

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