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MINI 08 - Prognostic/Predictive Biomarkers (ID 106)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:T.E. Stinchcombe, N. Pavlakis
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
MINI08.09 - Anti-Tumor Efficacy of Interleukin-27 in Non Small Cell Lung Cancer (ID 551)
16:45 - 18:15 | Author(s): G. Cipollone
Adenocarcinoma (AC) and Squamous Cell Carcinoma (SCC) constitute the commonest lung cancer histotypes, but current therapies still fail to significantly increase their survival rate. An effective immunotherapy to apply alternatively or together with specific treatments may be of great value. Here we asked whether Interleukin (IL)-27, which has revealed powerful antitumor activity in different tumor types and is toxicity-free in humans, is a promising therapeutic choice for NSCLC patients.
Human lung AC and SCC cell lines were used to assess IL-27’s effect on cancer cell viability, by flow cytometry, and on malignancy-related gene expression, by qRT-PCR. Its effects on tumor growth were assessed in pre-clinical models and examined histopathologically. Expression of IL-27Receptor(R) in clinical samples was assessed by laser capture microdissection followed by qRT-PCR, and by immunohistochemistry.
In vitro, IL-27 was ineffective on cancer cell proliferation or apoptosis, but fostered CXCL3/GROg/MIP2b expression. In vitro and in vivo, IL-27 down-regulated stemness-related genes, namely SONIC HEDGEHOG in AC cells, and OCT4A, SOX2, NOTCH1, KLF4 along with the Epithelial to Mesenchymal Transition (EMT)-related genes NESTIN, SNAI1/Snail, SNAI2/Slug and ZEB1, in SCC cells. In vivo, IL-27 hampered both AC and SCC tumor growth in association with a prominent granulocyte- and macrophage-driven colliquative necrosis, CXCL3 production, and a reduced pluripotency- and EMT-related gene expression. Myeloablation of tumor-bearing hosts mostly abolished IL-27's antitumor effects. In clinical samples, IL-27R was expressed by the majority of AC, 90%, and SCC, 84%. Its expression by the primary tumor was significantly associated with advanced stages of disease (P = 0,02) as assessed by Fisher’s exact test. IL-27R was also expressed by pre-cancerous lesions, microvessels, and by infiltrating immune cells as CD15[+]granulocytes, CD68[+]monocytes/macrophages and CD11c[+]myeloid dendritic cells scattered in the stroma or within the lymph node–like structures, known as tertiary-lymphoid-structures (TLS).
Altogether, our results highlight novel aspects of IL-27’s antitumor potential, specifically in NSCLC, such as the ability to drive myeloid cells towards antitumor activities, and down-regulate stemness genes, particularly in SCC cells, thus suppressing their self-renewal potential. IL-27 may thus be proposed for clinical trials with the prospect of its clinical use in immune-defective or advanced NSCLC patients.
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