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Deciphering the tumor-immune-microenvironment profile and organization within the tumors of melanoma patients undergoing immunotherapy

Project description

Tumour cells, tumour microenvironment and immune system interplay

Cancer progression is a complex process that depends on the interplay between tumour cells, tumour microenvironment and the immune system. In order to better understand tumour biology and response to treatment, it is necessary to profile protein expression of the whole interconnected system. Multiplexed ion beam imaging by time of flight (MIBI-TOF) is a technology in which antibodies conjugated to metals are used to simultaneously visualise dozens of proteins in intact tissue samples by secondary ion mass spectrometry. The EU-funded MelImmuneOrg project aims to uncover the immune profile and organisation within the tumours of melanoma patients undergoing immunotherapy using MIBI-TOF. The objectives are to analyse the intratumour heterogeneity and the genetic correlations between tumour, immune microenvironment and response to therapy.

Objective

Cancer progression is a complex process that depends on the interplay between tumor cells, tumor microenvironment, and the immune system. Inhibiting immunosuppression is beneficial for cancer patients. Although these therapies are promising they are successful only in part of the patients. Tumors are composed of distinct cell types with different phenotypes, that influence the efficacy of immunotherapies. Therefore, in order to better understand tumor biology and response to treatment, it is necessary to profile protein expression while preserving spatial information. Multiplexed Ion Beam Imaging by Time of Flight (MIBI-TOF) is a method in which antibodies conjugated to metals are used to simultaneously visualize dozens of proteins in intact tissue specimens by secondary ion mass spectrometry. Here we suggest to uncover the immune profile and organization within the tumors of melanoma patients undergoing immunotherapy using MIBI-TOF. My first objective is to characterize the tumor-immune microenvironments to understand how these are structured across patients and discover predictive features of response to immunotherapies. My second objective is to analyze the intratumor heterogeneity (ITH) of melanoma patients by exome sequencing. I will examine whether there are genetic correlates between ITH, immune microenvironment and response to therapy. Finally, my third objective will be the manipulation of individual hits to test their functional significance in tumor-immune architecture in murine models. By joining Dr. Keren’s lab that masters the MIBI-TOF technology, I will acquire this state-of-the art technique, as well as develop lab management and organization skills, and I will meet leader scientists from the immune-oncology field. This proposal will promote my competitiveness to gain an independent researcher position.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

WEIZMANN INSTITUTE OF SCIENCE
Net EU contribution
€ 185 464,32
Address
HERZL STREET 234
7610001 Rehovot
Israel
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 185 464,32