Time-series blood cytokine profiles correlate with treatment responses in triple-negative breast cancer patients

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发表日期：

2024年1月18日

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Don Pietro Saldajeno,
Shinpei Kawaoka,
Norikazu Masuda,
Sunao Tanaka,
Hiroko Bando,
Tomomi Nishimura,
Takayuki Kadoya,
Takashi Yamanaka,
Shigeru Imoto,
Ravindranath M. Velaga,
Nobuko Tamura,
Tomoyuki Aruga,
Kazushi Ikeda,
Yukiko Fukui,
Yurina Maeshima,
Masahiro Takada,
Eiji Suzuki,
Takayuki Ueno,
Seishi Ogawa,
Hironori Haga,
Shinji Ohno,
Satoshi Morita,
Kosuke Kawaguchi,
Masakazu Toi

摘要

Background

Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype. Partly due to its heterogeneity, it is currently challenging to stratify TNBC patients and predict treatment outcomes.

Methods

In this study, we examined blood cytokine profiles of TNBC patients throughout treatments (pre-treatment, during chemotherapy, pre-surgery, and 1 year after the surgery in a total of 294 samples). We analyzed the obtained cytokine datasets using weighted correlation network analyses, protein-protein interaction analyses, and logistic regression analyses.

Results

We identified five cytokines that correlate with good clinical outcomes: interleukin (IL)-1α, TNF-related apoptosis-inducing ligand (TRAIL), Stem Cell Factor (SCF), Chemokine ligand 5 (CCL5 also known as RANTES), and IL-16. The expression of these cytokines was decreased during chemotherapy and then restored after the treatment. Importantly, patients with good clinical outcomes had constitutively high expression of these cytokines during treatments. Protein-protein interaction analyses implicated that these five cytokines promote an immune response. Logistic regression analyses revealed that IL-1α and TRAIL expression levels at pre-treatment could predict treatment outcomes in our cohort.

Conclusion

We concluded that time-series cytokine profiles in breast cancer patients may be useful for understanding immune cell activity during treatment and for predicting treatment outcomes, supporting precision medicine.

Trial registration

The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (http://www.umin.ac.jp/ctr/index-j.htm) with the unique trial number UMIN000023162. The association Japan Breast Cancer Research Group trial number is JBCRG-22. The clinical outcome of the JBCRG-22 study was published in Breast Cancer Research and Treatment on 25 March 2021. https://doi.org/10.1007/s10549-021-06184-w.