739P - Penile squamous cell carcinoma tissue associated macrophages captured by multiplex immunfluorence are associated with clinical outcomes

Background

Penile squamous cell carcinoma (PSCC) is rare and the immune enviroment of PSCC remains poorly characterized. In this study, we characterize the immune microenvironment using multiplex immunofluorescence (mIF) and image analysis approaches in 57 patients with PSCC.

Methods

Representative tissue microarrays blocks of 57 patients with primary PSCC treated at H. Lee Moffitt Cancer Center (Tampa, FL) were stained for 10 immune markers: CD20, CD3, CD4, CD8, CD45RO, CD68, CD206, CD163, NKp46, FOXP3. Two experienced pathologists using an image analysis system divided each tissue core into tumor and stroma compartments and assessed the densities of cell phenotypes.For analyses focusing on overall survival (OS) we used Cox regression and Log-rank test for Kaplan-Meier plots. The maximally selected rank statistics test was used to identify cut-points of continuous variables with maximal discriminatory value for clinical outcomes.

Results

57 PSCC patients were included with median age 60 [IQR, 53-73]). 25 (44%) were pathologic stages 1-2, 25 (44%) were stage 3, and 7 (12%) were stage 4. 34 (60%) were HPV-negative. We did not observe significant differences in cell densities as defined by mIF in HPV(+) compared to HPV(–) PSCC. In univariable analysis, higher density of CD8+ cells in the tumor and stroma were associated with inferior median OS (36.6 months [95% CI, 19.0-84.1] vs 161.7 months [95% CI, 16.2-161.7]). Similarly, greater infiltration by tumor-associated (M2) macrophages in the tumor and stroma (CD68+CD163+CD206+) were associated with inferior median OS (13.3 months [95% CI, 1.0-not estimable) vs 80.1 months [95% CI, 27.1-161.2]. In Cox regression controlling for pathologic stage and M2 density as a continuous variable, the latter remained significantly associated with OS.

Conclusions

Multiplex image analysis of primary PSCC found no difference in the immune contexture of HPV(+) and HPV(-) patients. High levels of tumor-associated macrophages M2 was associated with inferior survival outcomes. Further characterization of T-cell subsets to gauge the exhausted status of T-cells is underway to explain the paradoxical effect noted, similar to that in kidney cancer immune environment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

J. Chahoud.

Funding

Has not received any funding.

Disclosure

S. Eschrich: Financial Interests, Personal, Member of Board of Directors: Cvergenx. P. Spiess: Non-Financial Interests, Institutional, Trial Chair: NCCN; Non-Financial Interests, Institutional, Speaker, Consultant, Advisor: ASCO/EAU; Non-Financial Interests, Personal and Institutional, Ownership Interest: Global Society of Rare GU Tumors. All other authors have declared no conflicts of interest.