Abstract
Immunotherapy targeting the PD-1–PD-L1 axis yielded good results in treating different immunologically ‘‘hot’’ tumors. A phase II study revealed good therapeutic activity of pembrolizumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of PD-L1 in human PC samples and highlights the pre-analytical and interpretation variables. Interestingly, 29% acinar PCs, 7% ductal PCs, and 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohistochemistry. Different scoring methods or cut-off criteria were applied on variable specimen-types, evaluating tumors showing different clinic-pathologic features. The positivity rate of different PD-L1 antibody clones in tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding the single case tested for RM-320. The most tested clone was E1L3N, followed by 22C3 (most used for pembrolizumab eligibility), SP263, SP142, and 28-8, which gave the positivity rates of 35%, 11–41% (depending on different scoring systems), 6%, 3%, and 15%, respectively. Other clones were tested in <200 cases. The PD-L1 positivity rate was usually higher in tumors than benign tissues. It was higher in non-tissue microarray specimens (41–50% vs. 15%), as PC cells frequently showed heterogenous or focal PD-L1-staining. PD-L1 was expressed by immune or stromal cells in 12% and 69% cases, respectively. Tumor heterogeneity, inter-institutional preanalytics, and inter-observer interpretation variability may account for result biases.
Highlights
Prostatic carcinoma (PC) is one of the most common cancers in men, with a 5-year survival rate of 30% at advanced stage [1,2,3,4]
Haffner et al [66] found that benign atrophic glands were frequently PD-L1-positive
PD-L1 expression was rarely reported in benign prostatic tissue or hyperplasia in the remaining studies: Sharma et al, 1/201 (0.5%) cases [27,35]; Richter et al, 1/24 (4%) cases [55]; and Sun et al, 0/30 (0%) cases [13]
Summary
Prostatic carcinoma (PC) is one of the most common cancers in men, with a 5-year survival rate of 30% at advanced stage [1,2,3,4]. Immune checkpoint therapy targeting the PD-1–PD-L1 axis has yielded good results in the standard treatment of different immunologically “hot” tumors (such as pulmonary non-small cell carcinoma, renal or bladder cancer, melanoma, etc.). Immunologically “cold” neoplasms seem relatively resistant to immune checkpoint therapy in some series, as they may show a relatively low somatic mutation frequency and few tumor-infiltrating T cells [6,7,8]. Some studies have been performed on the usually “cold” metastatic castration-resistant prostate cancer (mCRPC), with limited results; treatment doses and schedules could be implemented, especially in selected subgroups of patients, and larger series of patients should be recruited [4,8]. A phase II study (KEYNOTE-199) seemed to reveal a good therapeutic activity of pembrolizumab (an anti-PD-1 antibody) in monotherapy, and the 2021 United States National Comprehensive Cancer Network (NCCN) guidelines have allowed the use of this drug in selected PC-patients [4,9]
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