J. V. Meyers1, S. Sen1, A. J. Tatar1, A. Contreras1, P. Srinand1, C. S. Cho1 1University Of Wisconsin,Section Of Surgical Oncology,Madison, WI, USA
Introduction: Previous studies in primary colorectal adenocarcinoma have suggested that intratumoral infiltration by memory T cells may be strongly protective against the likelihood of metastatic disease dissemination. The prevalence and prognostic significance of memory T cell infiltration within metastatic foci are unknown. We hypothesized that memory T cell infiltration within resected hepatic colorectal metastases would be associated with favorable oncological characteristics.
Methods: Frozen samples from resected hepatic colorectal adenocarcinoma metastases were obtained from a prospectively maintained and institutionally-approved tumor bank. Thawed samples were fixed and analyzed by hematoxylin/eosin staining and by immunochemical analysis for expression of CD3 and CD45RO. CD3 (T cell) and CD45RO (memory T cell) expression was quantified under low power magnification by two blinded observers using a two-tiered low versus medium/high grading system. Clinicopathological and survival data were obtained from a prospectively-maintained institutional database. The approximate risk of disease recurrence was stratified using the Memorial Sloan-Kettering Cancer Center Clinical Risk Score (CRS). Comparison of categorical variables was performed using chi-square analysis, and differences in Kaplan-Meier estimates of overall and recurrence-free survival were compared using the log-rank test.
Results: Samples from ten resected tumors were obtained for this preliminary analysis. Eight tumors exhibited medium/high CD3 expression and 6 tumors exhibited medium/high CD45RO expression. The prevalence of T cell infiltration was somewhat higher among patients with a CRS ≥ 2 (100%) than patients with a CRS < 2 (33%) (p=0.07). The prevalence of memory T cell infiltration was higher among patients with a CRS ≥ 2 (86%) than patients with a CRS < 2 (0%) (p=0.03). T cell and memory T cell infiltration were not associated with differences in overall or recurrence-free survival.
Conclusion: There is a high prevalence of memory T cell infiltration within resected hepatic colorectal adenocarcinoma metastases. Contrary to our hypothesis, intratumoral memory T cell infiltration alone is not obviously associated with differences in survival outcome, and its prevalence may be paradoxically higher in conditions of adverse tumor characteristics. Ongoing studies will explore the hypothesis that intrametastatic memory T cell infiltration may exert a protective influence that mitigates the prognostic impact of adverse tumor characteristics.