Demaria S, Volm M D, Shapiro R L, Yee H T, Oratz R, Formenti S C, Muggia F, Symmans W F
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Clin Cancer Res. 2001 Oct;7(10):3025-30.
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.
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.
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.
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.
乳腺癌新辅助化疗为分析肿瘤和/或宿主中的生物学因素创造了新的可能性,这些因素可能在治疗反应中发挥作用。在本研究中,我们分析了新辅助紫杉醇治疗后局部抗肿瘤免疫是否发生变化,以及它们是否与治疗反应相关。
新辅助化疗(紫杉醇,200mg/m²,每2周一次,共4次治疗)后进行确定性手术治疗。对25例患者治疗前和治疗后手术标本的组织学切片进行淋巴细胞浸润程度和肿瘤浸润淋巴细胞(TILs)存在情况的分析。还对25例患者中的10例在首次给予紫杉醇后肿瘤中的累积凋亡反应进行了研究。
大多数患者肿瘤中的治疗前淋巴细胞浸润极少,且与临床反应无关。在治疗前无TILs的患者中,疾病稳定的患者中有0/3(0%)在治疗后出现TILs,临床部分缓解的患者中有3/12(25%)出现,临床完全缓解且有病理残留疾病的患者中有4/6(67%)出现。这些与肿瘤细胞对首次剂量紫杉醇的凋亡反应相关。
这些结果表明,治疗后TILs的出现与新辅助紫杉醇治疗的临床反应相关。讨论了新辅助化疗可能导致抗肿瘤T细胞诱导的可能机制。免疫过程可能影响乳腺癌患者对新辅助治疗的反应。