QUANTITATIVE STUDIES OF THE CELLULAR IMMUNE RESPONSE IN CERVICAL CANCER

Using stereology we presented a method to obtain basic biological data on the in situ cellular immune response towards cancer. We estimated the density and frequency of immune cells of 10 different phenotypes in cone biopsies from patients with stage I cervical squamous cell carcinoma (APMIS 115: 1321-1330, 2007). Using this method, we performed a study to investigate differences in the primary in situ cellular immune response between patients with and without relapse of stage IB cervical squamous cell carcinona. We found significantly lower densities of CD3+, CD4+ and CD8+ cells (both intra- and peritumoral) in tissue from patients who had relapse (Gynecologic Oncology 108 (2008) 106-111). To validate the results, a cohort study including 102 patients treated for cervical squamous cell carcinoma stage IB and IIA between 1990 and 2000 at Aalborg Hospital, Denmark was carried out. The in situ cellular immune response was investigated with respect to densities of T-cells (CD3+), T helper/regulatory cells (CD4+) and cytotoxic T-cells (CD8+) in intra- and peritumoral tissue. We found an increase in the density of both CD3+ and CD8+ cells to decrease the hazard ratio for relapse of disease. The decrease in hazard ratio was highly significant for both intra- and peritumoral cells. The largest decrease in hazard ratio was found for peritumoral CD3+ cells and it was 0.27 when increasing the cell density from 795 to 2043 cells/mm2 (25 to 75 percentile). According to this study, a low density of particularly peritumoral CD3+ cells is associated with increased risk of relapse in squamous cell cervical cancer.