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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort
Margaret Cocks1, Diana Taheri2, Mark W Ball1
1Departments of Pathology, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, MD, 21231.
Abstract:
Penile squamous cell carcinoma (SCC) is primarily treated by surgical resection. Locally advanced and metastatic diseases require a multidisciplinary treatment approach. However, mortality and morbidity remain high, and novel molecular and immunotherapeutic targets are actively being sought. We investigated the expression of immune-checkpoint markers in penile cancers. Fifty-three invasive penile SCCs diagnosed between 1985 and 2013 were retrieved from our surgical pathology archives. Representative formalin-fixed, paraffin-embedded archival blocks were used for the construction of 2 high-density tissue microarrays. Tissue microarrays were stained with immunohistochemistry for PD-L1, FOXP3, CD8, and Ki-67. PD-L1 was investigated using rabbit monoclonal anti-PD-L1 antibody (Cell Signaling, Boston, MA; E1L3N, 1:100). Overall, 21 (40%) of 53 penile SCCs had positive PD-L1 expression. PD-L1 was expressed by a significant proportion of advanced penile SCC. Forty-four percent (15/34) of stage pT2 or more SCC and 38% (6/16) of tumors with lymph node metastasis were positive for PD-L1. PD-L1 expression did not correlate with patient age, tumor location, histologic subtype, tumor stage, anatomic depth of invasion, or tumor grade. FOXP3 expression in tumoral immune cells was found in 26 (49%) of 53 cases. FOXP3 expression in stromal immune cells correlated with tumor thickness (P = .0086). The ratio of CD8/FOXP3 was greater than 1 in 62% of cases in tumor-infiltrating immune cells and 34% of cases in stromal immune cells. Our current study is the largest to assess expression of PD-L1 in a clinically well-annotated North American cohort of penile SCC. Our findings support a rationale for targeting immune-checkpoint inhibitor pathways in advanced penile SCC.
Insights
Penile squamous cell carcinoma (SCC) shows PD-L1 expression in 40% of cases, particularly in advanced stages. This supports targeting immune-checkpoint inhibitors for better penile cancer treatment outcomes.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Penile squamous cell carcinoma (SCC) treatment relies on surgery, but advanced/metastatic disease has high mortality.
- Novel molecular and immunotherapeutic targets are needed for penile SCC.
- Immune-checkpoint markers are potential therapeutic targets.
Purpose of the Study:
- To investigate the expression of immune-checkpoint markers, specifically PD-L1, in penile SCC.
- To correlate PD-L1 expression with clinical and pathological features of penile SCC.
- To evaluate the potential of targeting immune-checkpoint pathways in advanced penile SCC.
Main Methods:
- Analysis of 53 invasive penile SCC cases from surgical pathology archives (1985-2013).
- Construction of high-density tissue microarrays.
- Immunohistochemical staining for PD-L1, FOXP3, CD8, and Ki-67.
Main Results:
- PD-L1 expression was observed in 40% (21/53) of penile SCC cases.
- PD-L1 expression was significant in advanced penile SCC (44% of pT2+ and 38% of node-positive tumors).
- PD-L1 expression did not correlate with age, location, subtype, stage, depth, or grade. FOXP3 expression correlated with tumor thickness.
Conclusions:
- PD-L1 is expressed in a substantial proportion of penile SCC, especially in advanced disease.
- Findings support the rationale for targeting immune-checkpoint inhibitor pathways in advanced penile SCC.
- This study represents the largest assessment of PD-L1 in a North American cohort of penile SCC.
