Research Papers:

Indoleamine-2,3-dioxygenase and Interleukin-6 associated with tumor response to neoadjuvant chemotherapy in breast cancer

Fangxuan Li _, Lijuan Wei, Shixia Li and Juntian Liu

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Oncotarget. 2017; 8:107844-107858. https://doi.org/10.18632/oncotarget.22253

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Fangxuan Li1,*, Lijuan Wei1,*, Shixia Li1 and Juntian Liu1

1Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China

*These authors have contributed equally to this work

Correspondence to:

Fangxuan Li, email: [email protected]

Juntian Liu, email: [email protected]

Keywords: Indoleamine-2,3-dioxygenase; Interleukin-6; neoadjuvant chemotherapy; breast cancer; clinical response

Received: June 13, 2017    Accepted: October 02, 2017    Published: November 01, 2017


Purpose: Indoleamine-2,3-dioxygenase (IDO) and Interleukin-6 (IL-6) contribute to poor therapeutic effects, tumor relapse and aggressive tumor growth. IDO and IL-6 incorporate a positive feedback signal loop to maintain IDO and IL-6 constitutive expression and facilitate tumor progression.

Results: IDO expression was associated with IL-6 expression and plasma IL-6 level (P<0.05). Concentrating on clinicopathological features prior neoadjuvant chemotherapy, both IDO expression and plasma IL-6 level were associated with clinical T stage and N stage (P<0.05). IL-6 expression was associated with clinical T stage (P=0.016). The co-expression of IDO/IL-6 was correlated with clinical T, N stage and estrogen receptor (ER) status (P<0.05). IDO, IL-6 expression, clinical T stage, pathological T stage, ER status and Luminal type were correlated with clinical response to neoadjuvant chemotherapy (P<0.05). Multivariate analysis showed that IDO expression were correlated with clinical response to neoadjuvant chemotherapy (P=0.034). IL-6 expression and pathological T stage were correlated with pCR (P<0.05). In the multivariate analysis, postoperative pathological T stage associated with pCR (P=0.041). In the prognostic analysis, only clinical T stage was significant correlated with overall survival (P=0.003).

Materials and Methods: 46 breast cancer patients received neoadjuvant chemotherapy enrolled in this study. Immunohistochemistry was applied for evaluating IDO and IL-6 expression in biopsy tissues prior neoadjuvant chemotherapy. Immunofluorescence was applied to observe the co-localization of IDO and IL-6. Serum IL-6 level was examined via ELISA. The associations between IDO, IL-6, Serum IL-6 level and clinicopathological features, response to neoadjuvant chemotherapy were analyzed.

Conclusion: IDO and IL-6 expression associated with advanced breast cancer and poor response to neoadjuvant chemotherapy.

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