Immunogenic tumor cell death induced by chemotherapy
in patients with breast cancer and esophageal squamous cell carcinoma

Aoto,Keita; Mimura,Kousaku; Okayama,Hirokazu; Saito,Motonobu; Chida,Shun; Noda,Masaru; Nakajima,Takahiro; Saito,Katsuharu; Abe,Noriko; Ohki,Shinji; Ohtake,Tohru; Takenoshita,Seiichi; Kono,Koji

doi:10.3892/or.2017.6097

Immunogenic tumor cell death induced by chemotherapy in patients with breast cancer and esophageal squamous cell carcinoma

Authors:
- Keita Aoto
- Kousaku Mimura
- Hirokazu Okayama
- Motonobu Saito
- Shun Chida
- Masaru Noda
- Takahiro Nakajima
- Katsuharu Saito
- Noriko Abe
- Shinji Ohki
- Tohru Ohtake
- Seiichi Takenoshita
- Koji Kono
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Affiliations: Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan, Department of Advanced Cancer Immunotherapy, Fukushima Medical University, Fukushima 960-1295, Japan
Published online on: November 14, 2017 https://doi.org/10.3892/or.2017.6097
Pages: 151-159
Copyright: © Aoto et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has been reported that chemo-radiotherapy can induce immunogenic tumor cell death (ICD), which triggers T-cell immunity mainly mediated by high-mobility group box 1 protein (HMGB1) and calreticulin. However, there is still limited information to support this theory relating to chemotherapy alone. In the present study, the expression of HMGB1 and calreticulin was evaluated by immunohistochemistry in pre-treatment biopsy specimens and surgically resected specimens, which were obtained from patients with breast cancer (n=52) and esophageal squamous cell carcinoma (ESCC) (n=8) who had been treated with neoadjuvant chemotherapy (NAC). We also analyzed HMGB1 and calreticulin expression in breast cancer cell lines treated with chemotherapeutic drugs. As a result, both HMGB1 and calreticulin expression levels were significantly upregulated after NAC in both breast cancer and ESCC tissues. However, no significant correlation was observed between HMGB1 expression and pathological response after NAC or between HMGB1 expression and patient survival. Furthermore, although overall survival in the high infiltration group of CD8-positive T cells was significantly superior to that in the low infiltration group in breast cancer patients, there were no correlations between the number of CD8-positive T cells and HMGB1 or calreticulin expression levels. In addition, chemotherapeutic drugs induced upregulation of HMGB1 and calreticulin in all tested cell lines. Our findings indicate that chemotherapy alone can significantly induce ICD regardless of the degree of pathological response after chemotherapy.

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