Calreticulin upregulation in cervical cancer tissues from patients after 10 GY radiation therapy
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Authors
Okada, Kohei
Sato, Hiro
Kumazawa, Takuya
Mori, Yasumasa
Permata, Tiara Bunga Mayang
Uchihara, Yuki
Noda, Shin-ei
Suzuki, Keiji
Ikota, Hayato
Yokoo, Hideaki
Issue Date
2022-12-27
Type
Article
Language
en_US
Keywords
Calreticulin Upregulation , Cervical Cancer Tissues , Gy Radiation Therapy
Alternative Title
Abstract
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.
Description
Citation
Okada, K., Sato, H., Kumazawa, T., Mori, Y., Permata, T. B. M., Uchihara, Y., Noda, S. E., Suzuki, K., Ikota, H., Yokoo, H., Gondhowiardjo, S., Nakano, T., Ohno, T., & Shibata, A. (2022). Calreticulin Upregulation in Cervical Cancer Tissues From Patients After 10 Gy Radiation Therapy. Advances in radiation oncology, 8(3), 101159. https://doi.org/10.1016/j.adro.2022.101159
Publisher
Advances in Radiation Oncology