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Journal of Cancer Research and Clinical Oncology

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01-09-2017 | Original Article – Cancer Research

Impact of intra-tumoral IL17A and IL32 gene expression on T-cell responses and lymph node status in breast cancer patients

Authors: Shreyas Bhat, Nilesh Gardi, Sujata Hake, Nirupama Kotian, Sharada Sawant, Sadhana Kannan, Vani Parmar, Sangeeta Desai, Amit Dutt, Narendra N. Joshi

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2017

Abstract

Purpose

Pro-inflammatory cytokines such as Interleukin-17A (IL17A) and Interleukin-32 (IL32), known to enhance natural killer and T cell responses, are also elevated in human malignancies and linked to poor clinical outcomes. To address this paradox, we evaluated relation between IL17A and IL32 expression and other inflammation- and T cell response-associated genes in breast tumors.

Methods

TaqMan-based gene expression analysis was carried out in seventy-eight breast tumors. The association between IL17A and IL32 transcript levels and T cell response genes, ER status as well as lymph node status was also examined in breast tumors from TCGA dataset.

Results

IL17A expression was detected in 32.7% ER-positive and 84.6% ER-negative tumors, with higher expression in the latter group (26.2 vs 7.1-fold, p < 0.01). ER-negative tumors also showed higher expression of IL32 as opposed to ER-positive tumors (8.7 vs 2.5-fold, p < 0.01). Expression of both IL17A and IL32 genes positively correlated with CCL5, GNLY, TBX21, IL21 and IL23 transcript levels (p < 0.01). Amongst ER-positive tumors, higher IL32 expression significantly correlated with lymph node metastases (p < 0.05). Conversely, in ER-negative subtype, high IL17A and IL32 expression was seen in patients with negative lymph node status (p < 0.05). Tumors with high IL32 and IL17A expression showed higher expression of TH1 response genes studied, an observation validated by similar analysis in the TCGA breast tumors (n=1041). Of note, these tumors were characterized by low expression of a potentially immunosuppressive isoform of IL32 (IL32γ).

Conclusion

These results suggest that high expression of both IL17A and IL32 leads to enhancement of T cell responses. Our study, thus, provides basis for the emergence of strong T cell responses in an inflammatory milieu that have been shown to be associated with better prognosis in ER-negative breast cancer.

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Title: Impact of intra-tumoral IL17A and IL32 gene expression on T-cell responses and lymph node status in breast cancer patients
Authors: Shreyas Bhat
Nilesh Gardi
Sujata Hake
Nirupama Kotian
Sharada Sawant
Sadhana Kannan
Vani Parmar
Sangeeta Desai
Amit Dutt
Narendra N. Joshi
Publication date: 01-09-2017
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 9/2017
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-017-2431-5

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Impact of intra-tumoral IL17A and IL32 gene expression on T-cell responses and lymph node status in breast cancer patients

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Purpose

Methods

Results

Conclusion

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