Abstract 2750: Prognostic impact of tumor infiltrating lymphocytes in the tumor microenvironment of vulvar squamous cell carcinoma

Abstract

Abstract The amount of tumor infiltrating lymphocytes (TILs) is an established prognostic feature in the cancer microenvironment of colorectal and breast cancers, but data are less clear for most other solid cancer types. To study the prognostic impact of TILs in vulvar squamous cell carcinomas, a cohort of 530 cancers was analyzed by immunohistochemistry for CD3 and CD8 positive cells (CD3+, CD8+). Automated digital image analysis was used to quantitate the densities of CD3+, and CD8+ TILs in the invasive margin and the tumor center. The average immune cell density was significantly higher in the invasive margin (CD3+: 1772±1105, CD8+: 769±644 cells/mm2) as compared to the center of the tumor (CD3+: 518±570, CD8+: 301±445 cells/mm2, p≤0.0001 each). Comparison with clinic-pathological data revealed a significant prognostic impact of CD3+ but not of CD8+ cell density and a stronger link with tumor phenotype and outcome for TILs at the invasive tumor margin as compared to the tumor center. Elevated densities of CD3+ cells within the invasive margin were significantly associated with a favorable pT stage (p=0.0012) and a prolonged overall (p=0.0025) and progression free survival (p=0.0231). A high CD3+ cell density in the tumor center was linked to overall (p=0.0457) and progression free survival (p=0.0266). Unsupervised clustering of CD3+/CD8+ cell densities identified 3 major subsets corresponding to the immune desert (sparse TILs at invasive margin and tumor center), immune excluded (high TIL numbers at invasive margin but low TIL counts in the tumor center), and immune inflamed phenotypes (high TIL numbers at invasive margins and tumor center). Survival analysis revealed a particularly poor prognosis for the immune desert phenotype for overall (p=0.0071) and progression free survival (p=0.0027). In summary, our data suggest a clinical utility of TIL quantification in vulva squamous cell cancer. Citation Format: Maximilian Lennartz, Niclas Christian Blessin, Ann-Christin Rolschewski, Ronald Simon, Guido Sauter, Ria Uhlig, Linn Wölber, Sven Mahner, Nikolaus de Gregorio, Rüdiger Klapdor, Matthias Kalder, Stefan Steurer, Waldemar Wilczak, Eike Burandt, Simon Kind. Prognostic impact of tumor infiltrating lymphocytes in the tumor microenvironment of vulvar squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2750.