Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy

Purpose: Neoadjuvant chemotherapy for breast cancer creates new possibiliti es for the analysis of biological factors in the tumor and/or host, which m ay play a role in the response to treatment. In this study we analyzed whet her changes in local antitumor immunity take place after neoadjuvant paclit axel therapy and if they correlate with response to treatment. Experimental Design: Neoadjuvant chemotherapy (paclitaxel, 200 mg/m2 q2w, 4 treatments) was followed by definitive surgical management. Histological s ections from the pre- and post-treatment surgical specimens of 25 patients were analyzed for the extent of lymphocytic infiltration and presence of tu mor infiltrating lymphocytes (TILs). The cumulative apoptotic response in t he tumor after the first dose of paclitaxel was also studied in 10 of 25 pa tients. Results: Pretreatment lymphocytic infiltrate in the tumor was minimal in th e majority of patients and showed no relationship with clinical response. I n the patients without TILs before treatment, development of TILs after tre atment was noted in 0/3 (0%) patients with stable disease, 3/12 (25%) patie nts with clinical partial response, and 4/6 (67%) patients with clinical co mplete response and pathological residual disease. These correlated with th e tumor cell apoptotic response to the first dose of paclitaxel. Conclusions: These results suggest that development of TILs after treatment correlates with clinical response to neoadjuvant paclitaxel therapy. The p ossible mechanism(s) whereby neoadjuvant chemotherapy may lead to induction of antitumor T cells is discussed. Immunological processes may influence t he response of breast cancer patients to neoadjuvant treatment.