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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1524861
This article is part of the Research Topic Precision Oncology in Checkpoint Immunotherapy: Leveraging Predictive Biomarkers for Personalized Treatment View all 11 articles
Prognostic significance of the inhibitory-to-stimulatory immune checkpoint ratio in patients with breast cancer
Provisionally accepted
Chuangang Tang 1
Xiang Hu 1 Dawei Hao 1 Tao Chen 2 Pei Wang 1
Changwen Li 1 Chengling Chen 1 Yongcheng Li 1 Xiaowen Hao 1
Zeng Yuan 3*- 1 Xuzhou Central Hospital, Xuzhou, China
- 2 Xuzhou Medical University, Xuzhou, Jiangsu Province, China
- 3 Qilu Hospital, Shandong University, Jinan, Shandong Province, China
Background: Accumulating evidences suggested that immune checkpoints (ICPs) played an important role in malignancies including breast cancer (BRCA). We aimed to investigate whether inhibitory-to-stimulatory immune checkpoint ratio (ISICPR) could be used as a prognostic marker for BRCA.Methods: BRCA patients were enrolled from The Cancer Genome Atlas (TCGA).Survival analysis was performed with Kaplan-Meier (KM) methods. X-tile was used to calculate the optimal cut-off values of ISICPRs. Univariate and multivariate Cox regression analysis were carried out to identify prognostic factors for BRCA patients.Tissue microarray was used to validate our findings.In total, 586 BRCA patients were collected, including 104 cases of stage I, 330 of stage II, 139 of stage III, and 13 of stage IV. Univariate analysis showed that four ISICPRs (PDCD1/CD27 ratio, PDCD1/TNFSF4 ratio, IDO1/TMIGD2 ratio, and IDO1/TNFSF4 ratio) were significantly associated with the survival of BRCA patients.After adjusting for confounders, multivariate analysis indicated that only the IDO1/TMIGD2 ratio was an independent prognostic factor. The optimal cut-off values for the IDO1/TMIGD2 ratio were set at 4.4 and 6.3. Survival analysis indicated that the high-ratio group (ratio > 6.3) had a worse prognosis than both the low-ratio (ratio < 4.4) and medium-ratio group (4.4 < ratio < 6.3) (P < 0.001), which was further validated by BRCA tissue microarray.We found that IDO1/TMIGD2 ratio was an independent prognostic factor for BRCA. On one hand, dual targeting of IDO1 and TMIGD2 may be a more effective therapeutic strategy for patients with a high IDO1/TMIGD2 ratio. On the other hand, ISICPR was a promising indicator with high clinical values and worthy of further promotion in other cancers.
Keywords: breast cancer, TCGA, prognosis, IDO1, TMIGD2
Received: 08 Nov 2024; Accepted: 07 Feb 2025.
Copyright: © 2025 Tang, Hu, Hao, Chen, Wang, Li, Chen, Li, Hao and Yuan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zeng Yuan, Qilu Hospital, Shandong University, Jinan, 250012, Shandong Province, China
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