Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy

Author:

Someya Masanori1ORCID,Tsuchiya Takaaki1,Fukushima Yuki1,Hasegawa Tomokazu1,Takada Yu2,Hori Masakazu1,Miura Katsutoshi3,Kitagawa Mio3,Gocho Toshio1,Hirohashi Yoshihiko4,Torigoe Toshihiko4,Iwasaki Masahiro5,Matsuura Motoki5,Saito Tsuyoshi5,Sakata Koh-ichi1

Affiliation:

1. Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan

2. Department of Radiation Oncology, Sapporo City General Hospital, Sapporo, Japan

3. Department of Radiation Oncology, Teine Keijinkai Hospital, Sapporo, Japan

4. Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan

5. Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan

Abstract

Abstract Objective To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients. Methods We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues. Results In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is <70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230. Conclusion The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.

Funder

JSPS KAKENHI

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Radiology, Nuclear Medicine and imaging,Oncology,General Medicine

Reference25 articles.

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2. Association between radiotherapy-induced alteration ofeprogrammed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy;Tsuchiya;Strahlenther Onkol,2020

3. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy;Topalian;Nat Rev Cancer,2016

4. Pillars article: Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol 2003. 4: 330-336;Fontenot;J Immunol,2017

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