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

Article type: Research Article

Authors: Itoi, Naoko^a | Umeda, Tomoko^{a; b; c;} | Ishida, Mitsuaki^d | Murata, Satoshi^a | Mori, Tsuyoshi^a | Kawai, Yuki^a | Tomida, Kaori^a | Shimizu, Tomoharu^a | Kushima, Ryoji^e | Tani, Masaji^a

Affiliations: [a] Department of Surgery, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan | [b] Consortium for Community Medicine, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan | [c] Department of Breast surgery, Japan Community Healthcare Organization (JCHO) Shiga Hospital, 16-1 Fujimidai, Shiga, 520-0846, Japan | [d] Department of Pathology and Laboratory Medicine, Kansai Medical University, 2-3-1, Shin-machi, Hirakata, Osaka, 573-1191, Japan | [e] Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan

Correspondence: [*] Corresponding author: Tomoko Umeda, MD, PhD, Consortium for Community Medicine, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan. Tel.: +81 548 2238; Fax: +81 548 2240; E-mail: [email protected]

Note: [ 1 ] This article received a correction notice (Erratum) with the reference https://content.iospress.com/articles/breast-disease/bd190429.

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.

Keywords: Breast carcinoma, HER2, trastuzumab, tumor-infiltrating lymphocyte, immunohistochemistry

DOI: 10.3233/BD-180350

Journal: Breast Disease, vol. 38, no. 2, pp. 57-65, 2019