Roswell Park Comprehensive Cancer Center, Buffalo, NY
Yuanquan Yang , Kristopher Attwood , Cassandra Versaggi , Angela Omilian , Wiam Bshara , Bo Xu , Eric Kauffman , James Mohler , Khurshid Guru , Qiang Li , Saby George , Per Basse , Carl Morrison , Antonios Papanicolau-Sengos , Pawel Kalinski , Gurkamal S. Chatta
Background: High CD8+ tumor infiltrating lymphocytes (TILs) are associated with improved survival in many solid tumors. However, its prognostic value in prostate cancer (PCa) is unclear. Methods: Tumor microarrays of 290 patients with localized PCa who underwent radical prostatectomy (RP) at Roswell Park Comprehensive Cancer Center were retrospectively analyzed using immunohistochemistry. High risk patients were preferentially included to ensure adequate post-RP events for correlation. Six malignant and three benign cores from each patient were stained with anti-CD8 antibody (Dako, M7103). CD8+ cells were scored using Aperio (Leica Biosystems). Patients with < 5-year follow-up were excluded. The CD8+ cell density was dichotomized at 25th percentile. Clinical outcomes collected from a prospective quality assurance database were compared in high vs low TIL group. PSA persistence and recurrence were defined using NCCN prostate cancer guidelines. Results: 230 patients with median age 61 years met follow-up requirement. There were no significant differences in age, Gleason sum (GS), diagnostic PSA, margin status and pTNM stage between high vs low TIL group. High TILs were associated with improved 5-year overall survival (OS) (98% vs 91%, p = 0.008) and PCa-specific survival (99% vs 95%, p = 0.041) when compared to low TILs. High intratumoral/benign CD8 ratio ( > 1) was associated with improved metastasis-free survival (p = 0.031). The median biochemical recurrence (BCR)-free survival was longer in high TIL group (62 vs 42 m). However, statistical significance was not reached (p = 0.18). The prognostic import of high TILs was independent of surgical pathology. In subgroup analysis, it was also associated with improved 5-year OS (97% vs 88%, p = 0.042) in GS > 7 or pT3/4 patients (n = 149, 65%) and prolonged BCR-free survival (NR vs 58 months, p = 0.036) in GS < = 7 and < = pT2 patients. In contrast, the CD8 density of benign cores was not associated with clinical outcomes. Conclusions: High CD8+ TILs are independently associated with improved survival after RP in this majority of high-risk PCa population. This observation suggests that immunomodulation aimed at promoting CD8+ TILs may be beneficial.
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