Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

FP7

NKG2D Sintesi della relazione

Project ID: 331255
Finanziato nell'ambito di: FP7-PEOPLE
Paese: Austria

Periodic Report Summary 1 - NKG2D (CO-OPTION OF THE NKG2D LYMPHOCYTE RECEPTOR AS AN ONCOPROTEIN PROMOTING CANCER STEM CELL TRANSDIFFERENTIATION AND CANCER AUTONOMY)

A summary description of the project objectives

In this summary we report the research activities performed by Dr. Julia Kargl during her outgoing phase of the Marie-Curie IOF 331255 at the Fred Hutchinson Cancer Research Center, Seattle, USA. The research deviated somewhat from the original proposed project due to work published by other groups in the first six months of the fellowship. The major focus of the work during the outgoing phase was on: (a) Immune Cell Phenotypes in Non-Small Cell Lung Cancer (NSCLC), (b) Targeted immune-based therapy for lung squamous cell carcinoma and (c) Tumour-infiltrating lymphocyte (TIL) therapy in NSCLC. Dr. Houghton supervised the outgoing phase of the project.

A description of the work performed since the beginning of the project

Lung cancer is the leading cause of cancer deaths worldwide, with ~15% of lung cancer patients surviving for five years. Recent approaches in cancer therapy target immunosuppressive factors in the tumour microenvironment (TME) capable of derailing an effective immune response, using checkpoint inhibitors (e.g. anti-PD-1/PDL-1). Unfortunately, only ~20% of patients benefit from these treatments and appropriate studies are of importance to determine the underlying molecular mechanisms.
Lung cancer is a heterogeneous disease classified by multiple histologic subtypes, with adenocarcinoma (ADCA) and squamous cell carcinoma (SCCA) representing the majority of non-small cell lung cancer (NSCLC). To evaluate the complexity of the immune cell composition of the TME of human NSCLC the fellow examined tumour and non-adjacent lung tissue from the same patients. Tissue specimen from 73 individuals with corresponding clinicopathologic information were analysed by flow cytometry and immunohistochemistry. Next generation sequencing for T-cell receptors (TCR) was performed to assess the TCR repertoire and whole exome sequencing (WES) was performed to analyse mutational burden. In addition tumour infiltrated lymphocytes (TILs) were cultured and functionally tested.

A description of the main results achieved so far

The fellow pioneered a molecular characterization of the tumour microenvironment of non-small cell lung cancer using flow cytometry, TCR sequencing and WES to profile the non-malignant component of the tumour. She has demonstrated that the immune cell composition is unique for lung squamous cell carcinoma (SCCA) compared to lung adenocarcinoma (ADCA), which supports the development of targeted immune based therapies and should drive the direction of future research in this area.

The expected final results and their potential impact and use (including the socio-economic impact and the wider societal implications of the project so far).

As more immunotherapy agents will be available in the near future it will be of importance to know the immune cell composition of individual patients or tumour subtypes prior to immune checkpoint inhibitor treatment to be able to make logical treatment decisions leading to higher success rates. These data provide evidence that the immune cell composition present within different NSCLC subtypes displays unique phenotypes and identifying the immunosuppressive factors in different subsets will be important for successful immune-based therapy.

Contatto

Carolin Auer, (Director of Research Management Unit)
Tel.: +43 316 385 72016
Fax: +43 316 38572030
E-mail

Argomenti

Life Sciences
Numero di registrazione: 182148 / Ultimo aggiornamento: 2016-05-25
Fonte d'informazione: SESAM