Calreticulin Upregulation in Cervical Cancer Tissues From Patients After 10 Gy Radiation Therapy

Kohei Okada, MD; Hiro Sato, MD, PhD; Takuya Kumazawa, MD, PhD; Yasumasa Mori, MD, PhD; Tiara Bunga Mayang Permata, MD, PhD; Yuki Uchihara, PhD; Shin-ei Noda, MD, PhD; Keiji Suzuki, PhD; Hayato Ikota, MD, PhD; Hideaki Yokoo, MD, PhD; Soehartati Gondhowiardjo, MD, PhD; Takashi Nakano, MD, PhD; Tatsuya Ohno, MD, PhD; Atsushi Shibata, PhD

Advances in Radiation Oncology (May 2023)

Calreticulin Upregulation in Cervical Cancer Tissues From Patients After 10 Gy Radiation Therapy

Kohei Okada, MD,
Hiro Sato, MD, PhD,
Takuya Kumazawa, MD, PhD,
Yasumasa Mori, MD, PhD,
Tiara Bunga Mayang Permata, MD, PhD,
Yuki Uchihara, PhD,
Shin-ei Noda, MD, PhD,
Keiji Suzuki, PhD,
Hayato Ikota, MD, PhD,
Hideaki Yokoo, MD, PhD,
Soehartati Gondhowiardjo, MD, PhD,
Takashi Nakano, MD, PhD,
Tatsuya Ohno, MD, PhD,
Atsushi Shibata, PhD

Affiliations

Kohei Okada, MD: Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
Hiro Sato, MD, PhD: Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan; Corresponding authors: Hiro Sato, MD, PhD and Tatsuya Ohno, MD, PhD
Takuya Kumazawa, MD, PhD: Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan; Department of Radiation Oncology, Saku Central Hospital Advanced Care Center, Nakagomi, Saku, Nagano, Japan
Yasumasa Mori, MD, PhD: National Institute of Radiological Sciences, National Institute for Quantum and Radiological Science and Technology, Anagawa, Inage, Chiba, Japan
Tiara Bunga Mayang Permata, MD, PhD: Department of Radiation Oncology, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Yuki Uchihara, PhD: Signal Transduction Program, Gunma University Initiative for Advanced Research (GIAR), Gunma University, Maebashi, Gunma, Japan
Shin-ei Noda, MD, PhD: Department of Radiation Oncology, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Saitama, Japan
Keiji Suzuki, PhD: Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Sakamoto, Nagasaki, Japan
Hayato Ikota, MD, PhD: Clinical Department of Pathology, Gunma University Hospital, Maebashi, Gunma, Japan
Hideaki Yokoo, MD, PhD: Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
Soehartati Gondhowiardjo, MD, PhD: Department of Radiation Oncology, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Takashi Nakano, MD, PhD: National Institute of Radiological Sciences, National Institute for Quantum and Radiological Science and Technology, Anagawa, Inage, Chiba, Japan
Tatsuya Ohno, MD, PhD: Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan; Corresponding authors: Hiro Sato, MD, PhD and Tatsuya Ohno, MD, PhD
Atsushi Shibata, PhD: Signal Transduction Program, Gunma University Initiative for Advanced Research (GIAR), Gunma University, Maebashi, Gunma, Japan

Journal volume & issue: Vol. 8, no. 3
p. 101159

Abstract

Read online

Purpose: Understanding the immune response during radiation therapy (RT) in a clinical setting is imperative for maximizing the efficacy of combined RT and immunotherapy. Calreticulin, a major damage-associated molecular pattern that is exposed on the cell surface after RT, is presumed to be associated with the tumor-specific immune response. Here, we examined changes in calreticulin expression in clinical specimens obtained before and during RT and analyzed its relationship with the density of CD8+ T cells in the same patient set. Methods and Materials: This retrospective analysis evaluated 67 patients with cervical squamous cell carcinoma who were treated with definitive RT. Tumor biopsy specimens were collected before RT and after 10 Gy irradiation. Calreticulin expression in tumor cells was evaluated via immunohistochemical staining. Subsequently, the patients were divided into 2 groups according to the level of calreticulin expression, and the clinical outcomes were compared. Finally, the correlation between calreticulin levels and density of stromal CD8+ T cells was evaluated. Results: The calreticulin expression significantly increased after 10 Gy (82% of patients showed an increase; P < .01). Patients with increased calreticulin levels tended to show better progression-free survival, but this was not statistically significant (P = .09). In patients with high expression of calreticulin, a positive trend was observed between calreticulin and CD8+ T cell density, but the association was not statistically significant (P = .06). Conclusions: Calreticulin expression increased after 10 Gy irradiation in tissue biopsies of patients with cervical cancer. Higher calreticulin expression levels are potentially associated with better progression-free survival and greater T cell positivity, but there was no statistically significant relationship between calreticulin upregulation and clinical outcomes or CD8+ T cell density. Further analysis will be required to clarify mechanisms underlying the immune response to RT and to optimize the RT and immunotherapy combination approach.

Published in Advances in Radiation Oncology

ISSN: 2452-1094 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General): Medical physics. Medical radiology. Nuclear medicine; Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/advances-in-radiation-oncology/

About the journal