TY - JOUR
T1 - Calreticulin Upregulation in Cervical Cancer Tissues From Patients After 10 Gy Radiation Therapy
AU - Okada, Kohei
AU - Sato, Hiro
AU - Kumazawa, Takuya
AU - Mori, Yasumasa
AU - Permata, Tiara Bunga Mayang
AU - Uchihara, Yuki
AU - Noda, Shin ei
AU - Suzuki, Keiji
AU - Ikota, Hayato
AU - Yokoo, Hideaki
AU - Gondhowiardjo, Soehartati
AU - Nakano, Takashi
AU - Ohno, Tatsuya
AU - Shibata, Atsushi
N1 - Funding Information:
The authors thank Dr Yuya Yoshimoto (Fukushima Medical University, Fukushima; Gunma University, Maebashi, Japan) for his assistance in performing the immunohistochemical analysis. The authors thank Mr Koji Isoda (Gunma University, Maebashi, Japan) for his technical assistance in performing the immunohistochemical analysis.
Funding Information:
Sources of support: This study was supported by JSPS KAKENHI (grant nos. JP21H03596, JP17H04713, and JP19K08195), the Takeda Science Foundation, the Uehara Memorial Foundation, the Astellas Foundation for Research on Metabolic Disorders, The Kanae Foundation for the Promotion of Medical Science, the Yasuda Memorial Medicine Foundation, and the Nakajima Foundation. This study was also supported by the Program of the Network‐Type Joint Usage/Research Centre for Radiation Disaster Medical Science of Hiroshima University, Nagasaki University, Fukushima Medical University, and the grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan for programs for Leading Graduate Schools, Cultivating Global Leaders in Heavy Ion Therapeutics and Engineering.
Publisher Copyright:
© 2023 The Authors
PY - 2023/5/1
Y1 - 2023/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85147202922&partnerID=8YFLogxK
U2 - 10.1016/j.adro.2022.101159
DO - 10.1016/j.adro.2022.101159
M3 - Article
AN - SCOPUS:85147202922
SN - 2452-1094
VL - 8
JO - Advances in Radiation Oncology
JF - Advances in Radiation Oncology
IS - 3
M1 - 101159
ER -
