The Homicsko laboratory aims to be at the interface between clinical and translational research. The laboratory has four main themes: 1. Decomposition of tumor and systemic immunity in human samples of real-world data and clinical studies for biomarker development and precision medicine. 2. Ex vivo drug testing in patient-derived organoids/tumoroids. 3. Liquid biopsy approaches for guiding precision medicine. 4. Preclinical drug testing in genetically engineered mouse models of cancer. In addition, the lab is closely linked to the Molecular Tumor Board (MTB) of the CHUV Department of Oncology. We focus mainly on melanoma, thoracic malignancies, hepatobiliary and digestive tract tumors. ...
Analysis of the tumor microenvironment of malignant pleural mesothelioma (MPM) for predictive biomarkers of PD-1 blockade.
In close collaboration with the European Thoracic Oncology Platform (ETOP, www.etop-eu.org), we are performing a multidimensional analysis of tumor and blood samples of patients treated within the phase III clinical trial PROMISE-MESO. The study included 144 patients with advanced MPM after the failure of first-line therapy, who were randomized to receive a PD-1 inhibitor (Pembrolizumab) or chemotherapy (link). We perform multiple assays, including multiplex IHC (mIHC) with advanced image analysis (HALO), whole exome sequencing (WES), FFPE RNA sequencing, spatial transcriptomics, blood RNA sequencing, and blood cytokine analysis. We specifically focus on the predictive values of immune checkpoint proteins (PD-1, PD-L1, VISTA etc.) on cell type subsets. In addition, we perform an integrated analysis of all markers using machine learning algorithms in collaboration with the Data Science Center of CHUV.
Other studies included in this track:
- ETOP – STIMULI, randomized study in small cell lung cancer patients, in collaboration with ETOP. Funding: Sophien Stiftung, Zurich
- PEMSYS: Systemic analysis of PEMBROLIZUMAB treatment in metastatic melanoma. Sponsor: CHUV, Funding: MSD
- Nivo71: Nivolumab off-label treatment in advanced cancer patients. Sponsor: CHUV, Funding: BMS
- Lag3 prevalence: Lag3 analysis in advanced tumors. Sponsor: CHUV, Funding: BMS
- BioMark, blood-based biomarkers of cancer immune therapy. Sponsor: CHUV, Funding: CHUV, Euraka EU grant
- LUD2014: Durvalumab in combination with liposomal doxorubicin in advanced ovarian cancer. Sponsor: CHUV, Funding: LICR
- Hepatocellular carcinoma real-world data. Sponsor: CHUV, Funding: Fondation Gonella
Ex vivo drug testing in patient-derived organoids/tumoroids.
The personalization of oncology therapies is currently based on static tumor-derived biomarkers. The ex vivo analysis of patient-derived organoids (PDOs) might provide insights into the best drugs and drug combinations matching the genomic status of patients’ tumors. To this end, and in conjunction with the molecular tumor board of the CHUV Department of Oncology, we attempt to develop PDOs for patients with the need for ex vivo validation of tumor sequencing. To date, we have succeeded in growing organoids from a range of tumor types, including colorectal cancer, lung cancer, breast cancer, sarcomas, melanoma, hepatocellular carcinoma, and biliary tumors.
ExTrace: Liquid biopsy approaches for guiding precision medicine
The advent of precision medicine also came with the possibility and need to monitor responses using non-invasive techniques. Our lab is interested in two main approaches for direct tumor monitoring: 1. Next-generation circulating cell-free DNA analysis and detection of circulating tumor cells. For both, we are collaborating with start-up companies to test and deliver the latest innovations to patient care.
In 2022, together with our partners Parithera and CSEM, we obtained a major grant by Innosuisse for the innovation project „ExTrace - Enabling single cell resolution analysis of cancer cells extracted from blood“, enabling us to move this technology ever closer to clinical practice.
Preclinical drug testing in genetically engineered mouse models of melanoma
The care of metastatic melanoma has been revolutionized by targeted and immune therapies. However, a large fraction of patients still succumbs to the disease. To tackle remaining challenges linked to treatment resistance, we make use of genetically engineered mouse models of melanoma that retain the complex microenvironment of human melanoma tumors. These models are resistant to both immune and targeted therapies. One such model, iBIP2, developed by the Hanahan laboratory, serves as a surrogate model to study response and resistance to targeted and immune therapies. We have a particular interest in repurposing already approved compounds for combination therapy of melanoma. In a next step, these therapies can potentially be translated to human clinical trials.
Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8+ T cells and reprogramming macrophages
Tichet M, Wullschleger S, Chryplewicz A, (...), Umaña P, Klein C, Hanahan D
Immunity – 2023 Jan 10
Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion.
Zeng Q, Saghafinia S, Chryplewicz A, (...), Tichet M, Homicsko K, Hanahan D
Science – 2022 Nov 18
First communication on the efficacy of combined 177Lutetium-PSMA with immunotherapy outside prostate cancer.
Digklia A, Boughdad S, Homicsko K, (...), Peters S, Prior J, Schaefer N
Journal for immunotherapy of cancer – 2022 Oct 10
Cancer cell autophagy, reprogrammed macrophages, and remodeled vasculature in glioblastoma triggers tumor immunity.
Chryplewicz A, Scotton J, Tichet M, (...), Joyce JA, Homicsko K, Hanahan D
Cancer Cell – 2022 Sep 15
Proton Pump Inhibitor Use and Efficacy of Nivolumab and Ipilimumab in Advanced Melanoma.
Homicsko K, Dummer R, Hoeller C, (...), Paulucci D, Dobler D, Michielin O
Cancers – 2022 May 5
Marina Alexandre Gaveta
Lab Technician, CHUV
Postdoctoral Fellow, Chief resident at the Service of Medical Oncology & Molecular Tumor Board, CHUV
Sylvie André Baflast
Lab Manager, CHUV
PhD Student in Computational Life Sciences, CHUV
Postdoctoral Fellow, CHUV
LICR Postdoctoral Fellow, Surgical Trainee, CHUV
Turning tumors from cold to inflamed to improve immunotherapy response.
Gerard CL, Delyon J, Wicky A, (...), Homicsko K, Cuendet MA, Michielin O
Cancer treatment reviews – 2021 May 19
Cancer Cells Retrace a Stepwise Differentiation Program during Malignant Progression.
Saghafinia S, Homicsko K, Di Domenico A, (...), Ciriello G, Michael IP, Hanahan D
Cancer discovery – 2021 Apr 28
Late-onset and long-lasting immune-related adverse events from immune checkpoint-inhibitors: An overlooked aspect in immunotherapy.
Ghisoni E, Wicky A, Bouchaab H, (...), Cuendet MA, Di Maio M, Michielin O
European journal of cancer (Oxford, England : 1990) – 2021 Apr 14
Organoid technology and applications in cancer immunotherapy and precision medicine.
Current opinion in biotechnology – 2020 Jun 27
High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays.
Brandenberg N, Hoehnel S, Kuttler F, (...), Coukos G, Turcatti G, Lutolf MP
Nature biomedical engineering – 2020 Jun 8
LBA2 – Proton pump inhibitors negatively impact survival of PD-1 inhibitor based therapies in metastatic melanoma patients
Homicsko K, Richtig G, Tuchmann F, (...), Holler C, Dafni C, Michielin OA
Annals of Oncology – 2020 Jan 7
Unsorted single-cell RNA sequencing profiles of metastatic melanoma patients reveal the heterogeneity of melanoma-associated fibroblasts
Homicsko K, Barras D, Lopez AV, (...), Coukos G, Hanahan D, Michielin OA
Annals of Oncology – 2019 Oct 1
Tumor lymphangiogenesis promotes T cell infiltration and potentiates immunotherapy in melanoma.
Fankhauser M, Broggi MAS, Potin L, (...), Hanahan D, Speiser DE, Swartz MA
Science translational medicine – 2017 Sep 13
Combine and Conquer: Double CTLA-4 and PD-1 Blockade Combined with Whole Tumor Antigen Vaccine Cooperate to Eradicate Tumors.
Homicsko K, Duraiswamy J, Doucey MA, Coukos G
Cancer research – 2016 Dec 1
Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082).
Wick W, Gorlia T, Bady P, (...), Lhermitte B, Pesce G, Hegi ME
Clinical cancer research : an official journal of the American Association for Cancer Research – 2016 May 3
Targeting Programmed Cell Death 1 in Ovarian Cancer.
Homicsko K, Coukos G
Journal of clinical oncology : official journal of the American Society of Clinical Oncology – 2015 Oct 26
The consensus molecular subtypes of colorectal cancer.
Guinney J, Dienstmann R, Wang X, (...), Kopetz S, Vermeulen L, Tejpar S
Nature medicine – 2015 Oct 12
MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial.
Weller M, Tabatabai G, Kästner B, (...), Reifenberger G, Wick W, DIRECTOR Study Group.
Clinical cancer research : an official journal of the American Association for Cancer Research – 2015 Feb 5
A colorectal cancer classification system that associates cellular phenotype and responses to therapy.
Sadanandam A, Lyssiotis CA, Homicsko K, (...), Cantley LC, Gray JW, Hanahan D
Nature medicine – 2013 Apr 14
Neoadjuvant and adjuvant strategies in renal cell carcinoma: more questions than answers.
Homicsko K, Berthold DR
Anti-cancer drugs – 2011 Jan