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


METHODS
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.
Demaria
S
S
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. sandra@phri.nyu.edu
Volm
M D
MD
Shapiro
R L
RL
Yee
H T
HT
Oratz
R
R
Formenti
S C
SC
Muggia
F
F
Symmans
W F
WF
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017252:CD3 Complex / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects*; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use*; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000032:analysis; D000074019:T-Cell Intracellular Antigen-1; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D017252:CD3 Complex; D016827:CD8 Antigens; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D017239:Paclitaxel