2022
DOI: 10.1080/2162402x.2022.2094133
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Homologous recombination repair deficient prostate cancer represents an immunologically distinct subtype

Abstract: Homologous recombination repair deficiency (HRD) is observed in 10% of patients with castrate-resistant prostate cancer (PCa). Preliminary data suggest that HRD-PCa might be more responsive to immune checkpoint inhibitors (ICIs). In this study, we compare the tumor immune landscape and peripheral T cell receptor (TCR) repertoire of patients with and without HRD-PCa to gain further insight into the immunogenicity of HRD-PCa. Immunohistochemistry was performed on tumor tissue of 81 patients, including 15 patient… Show more

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Cited by 6 publications
(3 citation statements)
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“…The higher levels of immunosuppressive immune cells infiltrating the tumor may explain the low response rates to immune checkpoint inhibition observed in patients with PC harboring CDK12 mutations. The findings of van Wilpe et al [ 77 ] support the view that PC with HRD should be considered an immunologically distinct subtype characterized by an altered peripheral T cell receptor repertoire. Although these findings suggest that CDK12 loss is associated with limited susceptibility to immune checkpoint inhibition in patients with PC, larger prospective clinical trials are required to determine the clinical value of immunotherapy in patients with CDK12 -mutant PC.…”
Section: Prognostic and Predictive Significance Of Hrrm In Pcmentioning
confidence: 84%
“…The higher levels of immunosuppressive immune cells infiltrating the tumor may explain the low response rates to immune checkpoint inhibition observed in patients with PC harboring CDK12 mutations. The findings of van Wilpe et al [ 77 ] support the view that PC with HRD should be considered an immunologically distinct subtype characterized by an altered peripheral T cell receptor repertoire. Although these findings suggest that CDK12 loss is associated with limited susceptibility to immune checkpoint inhibition in patients with PC, larger prospective clinical trials are required to determine the clinical value of immunotherapy in patients with CDK12 -mutant PC.…”
Section: Prognostic and Predictive Significance Of Hrrm In Pcmentioning
confidence: 84%
“…ITGB6 encoded the β6 integrin subunit, with significantly higher expression observed in metastatic castrate-resistant androgen receptor-negative prostate tumors compared to androgen receptor-positive tumors [ 72 ]. Approximately 10% of CRPC patients exhibited HRD, and patients with M1 stage, high Gleason score, and IDC-P pathology demonstrated higher HRD scores, which correlated with poor prognosis in PCa [ 73 , 74 ]. Consistently, we observed that subtype 1, associated with worse prognosis, exhibited a significantly higher HRD score than subtype 2.…”
Section: Discussionmentioning
confidence: 99%
“…For example, point mutations caused by dMMR contribute to the production of tumor neoantigens that facilitate tumor immune recognition [145]. Tumors with homologous recombinant repair defects represent higher genomic instability and responsiveness to immunotherapy [146,147]. DDR inhibitors can artificially augment DNA damage and generate DDR defects so that tumor immunogenicity and tumor sensitivity to immunotherapy are increased.…”
Section: Crosstalk Between the Dna Damage Response And Innate And Ada...mentioning
confidence: 99%