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

Clin Cancer Res. 2001 Oct;7(10):3025-30.

Abstract

Purpose: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study we analyzed whether changes in local antitumor immunity take place after neoadjuvant paclitaxel 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 sections from the pre- and post-treatment surgical specimens of 25 patients were analyzed for the extent of lymphocytic infiltration and presence of tumor infiltrating lymphocytes (TILs). The cumulative apoptotic response in the tumor after the first dose of paclitaxel was also studied in 10 of 25 patients.

Results: Pretreatment lymphocytic infiltrate in the tumor was minimal in the majority of patients and showed no relationship with clinical response. In the patients without TILs before treatment, development of TILs after treatment was noted in 0/3 (0%) patients with stable disease, 3/12 (25%) patients with clinical partial response, and 4/6 (67%) patients with clinical complete response and pathological residual disease. These correlated with the 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 possible mechanism(s) whereby neoadjuvant chemotherapy may lead to induction of antitumor T cells is discussed. Immunological processes may influence the response of breast cancer patients to neoadjuvant treatment.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / surgery
  • CD3 Complex / analysis
  • CD8 Antigens / analysis
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / drug effects*
  • Membrane Proteins / analysis
  • Middle Aged
  • Paclitaxel / therapeutic use*
  • Poly(A)-Binding Proteins
  • Proteins*
  • RNA-Binding Proteins / analysis
  • T-Cell Intracellular Antigen-1
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Phytogenic
  • CD3 Complex
  • CD8 Antigens
  • Membrane Proteins
  • Poly(A)-Binding Proteins
  • Proteins
  • RNA-Binding Proteins
  • T-Cell Intracellular Antigen-1
  • TIA1 protein, human
  • Paclitaxel