Research

My group focuses on understanding the molecular and cellular mechanisms that mediate resistance to chemotherapy, mainly in breast and ovarian cancer. Using state-of-the-art mouse models of cancer, as well as quantitative molecular and cellular approaches, we are interested in dissecting the microenvironmental cues that orchestrate specific tumour responses and metastasis formation after chemotherapy. More specifically, we are interested in understanding how inflammation - and tumour-associated myeloid cells in particular - is linked to chemoresistance, in order to develop new therapeutic approaches for the treatment of metastatic gynecological cancers. Current projects in the lab include:

• Investigating the role of extracellular matrix in myeloid cell recruitment and chemoresistance
• Identify the molecular and cellular mechanisms of extracellular vesicle secretion after taxane-based therapy
• Understanding how chemotherapy and chemotherapy-elicited extracellular vesicles modulate the function of myeloid cells in primary tumours and pre-metastatic niches
• Tumour-associated macrophage evolution during anti-cancer therapies

Other Activities

• Member of Hellenic Society of Biochemistry and Molecular Biology

Major Funding

• 2019-2022 - Barts Charity, Dissecting the tumour-host interactions in premetastatic niches during chemotherapy
• 2020-2023 - CRUK PhD studentship, Dissecting the role of periostin-myeloid cell interactions in mediating chemoresistance, £105,900

Recent Publications

O4 Mechanisms of lung cancer hyper-progression promoted by PD-1 immune checkpoint blockade Martinez-Usatorre A, Kadioglu E, Cianciaruso C et al. Journal for ImmunoTherapy of Cancer (2020) 8(10) a5.1-a5a5

Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models Keklikoglou I, Cianciaruso C, Güç E et al. Nature Cell Biology (2019) 21(7) 190-202

Periostin Limits Tumor Response to VEGFA Inhibition Keklikoglou I, Kadioglu E, Bissinger S et al. Cell Reports (2018) 22(7) 2530-2540

CSF1/CSF1R signaling blockade triggers release of matrix-degrading proteases in mouse models Bissinger S, Schmittnaegel M, Keklikoglou I et al. JOURNAL FOR IMMUNOTHERAPY OF CANCER (2017) 5(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000460207200090&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes Keklikoglou I, Hosaka K, Bender C et al. Oncogene (2015) 34(7) 4867-4878

Perivascular M2 macrophages stimulate tumor relapse after chemotherapy Hughes R, Qian BZ, Rowan C et al. Cancer Research (2015) 75(7) 3479-3491

MicroRNA-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer Shukla K, Sharma AK, Ward A et al. Molecular Oncology (2015) 9(7) 1106-1119

A distinct subset of perivascular macrophages drive tumour relapse after chemotherapy Russell H, Qian B, Keklikoglou I et al. CLINICAL & EXPERIMENTAL METASTASIS (2015) 32(11) 184-184
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000351601900012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Cancer: Metastasis risk after anti-macrophage therapy Keklikoglou I, De Palma M Nature (2014) 515(7) 46-47

Role of angiopoietin-2 in adaptive tumor resistance to VEGF signaling blockade Rigamonti N, Kadioglu E, Keklikoglou I et al. Cell Reports (2014) 8(7) 696-706

Biography

I studied Biology at Aristotle University of Thessaloniki (Greece). During my undergraduate studies, I trained with Prof George Mosialos to characterise the role of certain aminoacids of TRAF5 and TRAF6 molecules in NF-kB signalling activation. In 2008, I moved to Heidelberg (Germany) for my postgraduate studies in molecular and cellular biology at the Ruperto-Carola University of Heidelberg. I joined the laboratory of Prof Stefan Wiemann at the German Cancer Research Center (DKFZ) where I completed my PhD on the identification of novel miRNAs that regulate NF-kB signalling in breast and pancreatic cancer.

In 2012, driven by my curiosity and interest in understanding the role of tumour microenvironment in modulating tumour responses to therapies, I moved to Lausanne (Switzerland) to join the laboratory of Prof Michele De Palma at the Swiss Federal Institute of Technology (EPFL). During my postdoctoral training in De Palma’s lab I identified extracellular matrix- and vesicle-mediated mechanisms of resistance to anti-angiogenic and cytotoxic therapies, respectively, through alterations in the accumulation and function of tumour-associated myeloid cells.

In 2019 I moved to London to start my own lab at Barts Cancer Institute, Queen Mary University of London (UK) within the Centre for Tumour Microenvironment.