# Phenotypic alterations in immune cells and their association with toxicities in postoperative endometrial cancer patients undergoing brachytherapy

**Authors:** Naiping Sun, Jianting Liu, Zhulin Dong, Ruixin Suo, Junli Ren

PMC · DOI: 10.3389/fonc.2025.1578394 · Frontiers in Oncology · 2025-07-16

## TL;DR

This study examines how brachytherapy affects immune cells in endometrial cancer patients and links changes in NK and NKT cells to specific side effects like radiation proctitis.

## Contribution

The study identifies a novel association between elevated NK/NKT cell levels and acute radiation proctitis in brachytherapy-treated patients.

## Key findings

- NK and NKT cells increased significantly during and after brachytherapy, while B cells decreased.
- Higher NK cell levels correlated with a significantly higher incidence of acute radiation proctitis.
- Brachytherapy caused mild side effects with no grade II or higher toxicities observed.

## Abstract

This study aims to investigate the phenotypic alterations in peripheral blood immune cells, especially natural killer (NK) cells, natural killer T (NKT) cells, total B cells, total T cells and their subsets, in postoperative patients with intermediate-risk endometrial cancer undergoing brachytherapy, and explores their association with adverse reactions.

A cohort of ninety-two patients, who received brachytherapy (5.0 Gy per fraction, 6 fractions) at Shanxi Cancer Hospital from January 2022 to November 2024, was included in this study. Immune cell subsets, including CD45+CD3-CD16+CD56+ NK cells, CD3+CD56+ NKT cells, CD45+CD3-CD19+ B cells, CD3+CD8+ T cells, CD3+CD4+ CD4+ helper T cells, CD3+CD8+ Cytotoxic T cells, CD45+CD4-CD25HICD127LO Regulatory T cells, were quantified using flow cytometry pre-, during, and post- treatment. Various statistical methods were applied to analyze these phenotypic changes and the chi-square test was employed to explore their association with toxicities.

Compared to pre-treatment levels, NK cells and NKT cells increased significantly during and post-treatment (P<0.001, P=0.003), while B cells decreased significantly(P<0.001). No notable alterations were observed in the counts of total T cells and their subsets throughout the treatment process (P>0.05). Brachytherapy caused mild side effects, with no toxicities of grade II or higher observed. The incidence of acute radiation proctitis was significantly higher in the group with elevated NK cell levels compared to the non-elevated group (31.9% vs. 8.7%, P=0.028). The incidence of radiation proctitis, cystitis, and vaginitis did not differ significantly among the other groups (P>0.05).

Brachytherapy enhances innate immune activation through the upregulation of NK/NKT cells, potentially correlating with the development of acute proctitis. These findings highlight immune modulation as a prospective biomarker for managing radiotherapy-induced toxicity.

## Linked entities

- **Diseases:** endometrial cancer (MONDO:0002447), radiation proctitis (MONDO:0019084), cystitis (MONDO:0006032), vaginitis (MONDO:0002234)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, CGAS (cyclic GMP-AMP synthase) [NCBI Gene 115004] {aka C6orf150, D4, MB21D1, h-cGAS}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, FCGR3A (Fc gamma receptor IIIa) [NCBI Gene 2214] {aka CD16-II, CD16A, FCG3, FCGR3, FCRIIIA, FcGRIIIA}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, ISG20 (interferon stimulated exonuclease gene 20) [NCBI Gene 3669] {aka CD25, HEM45}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, IL7R (interleukin 7 receptor) [NCBI Gene 3575] {aka CD127, CDW127, IL-7R-alpha, IL-7Ralpha, IL7RA, IL7Ralpha}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}
- **Diseases:** Mixed carcinoma (MESH:D018198), Carcinosarcoma (MESH:D002296), inflammation (MESH:D007249), Cancer (MESH:D009369), Serous adenocarcinoma (MESH:D000230), vaginitis (MESH:D014627), radiation vaginitis (MESH:D014623), Clear cell adenocarcinoma (MESH:D018262), Undifferentiated carcinoma (MESH:D002277), acute proctitis (MESH:D011349), lung cancer (MESH:D008175), endometrial cancer (MESH:D016889), toxicities (MESH:D064420), chronic radiation cystitis (MESH:D011832), cystitis (MESH:D003556), acute and chronic radiation cystitis (MESH:D054508)
- **Chemicals:** 192Ir (MESH:C000615087), NaCl (MESH:D012965), KEYNOTE- (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12307430/full.md

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Source: https://tomesphere.com/paper/PMC12307430