Infiltration of CD4, CD8, CD56, and Fox-P3-positive lymphocytes in breast carcinoma tissue after neoadjuvant chemotherapy with or without trastuzumab1

Abstract

BACKGROUND: Trastuzumab (Tz) is assumed to prime antibody-dependent cellular cytotoxicity (ADCC); however, it remains unclear whether Tz therapy can clinically induce adaptive cellular immunity. OBJECTIVE: Adaptive Cellular Immune Effect of Tz Therapy. METHODS: This study included 29 surgical invasive breast carcinomas administered neoadjuvant chemotherapy with Tz (15 cases) or without Tz (14 cases). The numbers of immunoreactive cells (CD4, CD8, CD56, and Fox-P3) in three different compartments (intratumoral, adjacent stromal, and distant stromal) were determined. RESULTS: The average number of adjacent stromal CD4-positive, CD8-positive, and Fox-P3-positive cells in the Tz+ group was significantly greater than that in the Tz− group (p = 0.036, 0.0049, and 0.043, respectively). However, the number of Fox-P3-positive cells was much less than that of CD4-positive cells. Moreover, distant stromal CD4-positive and CD8-positive cells in the Tz+ group was also significantly greater than that of the Tz− group (p = 0.029 and 0.032, respectively). Only a small number of CD56-positive natural killer cells, playing a main role in ADCC, accumulated at the tumor site after Tz therapy. CONCLUSIONS: The results suggest that Tz therapy induces adaptive cellular immunity, including infiltration of both CD4-positive helper T cells and CD8-positive cytotoxic T cells into the breast carcinoma lesion.

Combination Immunotherapy Strategies in Breast Cancer

“…HER2 overexpression is found in 15-20% of invasive breast cancers and is associated with aggressive behavior and poor survival related to metastatic recurrence [32]. Targeted anti-HER2 treatments function by inhibiting intracellular signaling, but also by facilitating antibody-dependent cellular cytotoxicity (ADCC), which relies on both the innate and adaptive immune system [33][34][35]. Furthermore, anti-HER2 antibodies have been shown to synergize with anti-PD-1/L1 in mammary carcinoma models [36].…”