T Cell Infiltrate Predicts Long-Term Survival Following Resection of Colorectal Cancer Liver Metastases

Background. While tumor infiltrating lymphocytes (TIL) have been shown to independently predict survival in primary colorectal cancer, the prognostic implications of TIL in resectable colorectal cancer liver metastases (CRCLM) have not been previously defined. This study examines the correlation between TIL numbers and survival following hepatic resection. Methods. We studied patients who survived <= 2 or >= 10 years following CRCLM resection. Immunohistochemistry was performed on tissue microarrays (TMAs) to determine the number of T cells within CRCLM. Correlation between TIL frequency and <= 2 or >= 10 year survival was determined while controlling for established prognostic factors. Results. Of 162 patients, 104 survived <= 2 years and 58 survived >= 10 years. Independent correlates of 10-year survival following CRCLM resection included a high number of CD8 T cells, a low number of CD4 T cells, and a clinical risk score of <= 2 (P < 0.001). Among 10-year survivors, 31% of patients had a high number of CD8 T cells compared with 8% for <= 2 year survivors (P < 0.01). Surprisingly, only 22% of 10-year survivors had a high number of CD4 T cells, in contrast to 69% of those who died within 2 years (P < 0.001). The combination of CD8 and CD4 T cell counts was a more powerful predictor of survival than either marker alone. Conclusions. CRCLM T cell number is an independent correlate of long-term survival following liver resection. We conclude that CRCLM TIL analysis represents a potentially powerful prognostic tool which will require further validation prior to broad application.