Rebuzzi Sara Elena, Rescigno Pasquale, Catalano Fabio, Mollica Veronica, Vogl Ursula Maria, Marandino Laura, Massari Francesco, Pereira Mestre Ricardo, Zanardi Elisa, Signori Alessio, Buti Sebastiano, Bauckneht Matteo, Gillessen Silke, Banna Giuseppe Luigi, Fornarini Giuseppe
Medical Oncology Unit, Ospedale San Paolo, 17100 Savona, Italy.
Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genova, 16132 Genova, Italy.
Cancers (Basel). 2022 Feb 28;14(5):1245. doi: 10.3390/cancers14051245.
In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs.
在过去十年中，晚期前列腺癌（PCa）患者有了许多新的治疗选择，转移性疾病患者的生存期得以延长，不过该病仍无法治愈。对免疫检查点抑制剂（ICIs）的重视引发了该领域的多项试验，但目前结果令人失望。因此，我们讨论前列腺癌的免疫生物学，介绍正在进行的试验和现有临床数据，以了解免疫疗法是否可能成为这种疾病的有效选择，以及哪些患者亚组可能更易从中获益。当前证据表明，除前列腺肿瘤细胞的基因组决定因素外，肿瘤微环境需要进行定性而非定量评估。免疫疗法生物标志物（如PD-L1、肿瘤突变负荷（TMB）或错配修复缺陷（dMMR）/微卫星高度不稳定（MSI-H））的预后或预测价值在前列腺癌中需要进一步评估。免疫检查点抑制剂单药治疗效果一般。相比之下，与其他标准治疗（激素药物、化疗、聚（ADP-核糖）聚合酶（PARP）抑制剂、镭-223和酪氨酸激酶抑制剂（TKIs））联合的策略已显示出一些成果。免疫疗法应在生物标志物选择的患者中进行更好的研究，特别是具有特定通路异常的患者（例如，AR-V7变体、同源重组缺陷（HRD）、细胞周期蛋白依赖性激酶12（CDK12）失活肿瘤、MSI-H肿瘤）。最后，我们介绍前列腺癌中可能调节肿瘤微环境并通过免疫检查点抑制剂提高抗肿瘤活性的新潜在靶点。
