world-immunology-cancer-summit-2019-posters

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Volume 02

Journal of Immune Disorders & Therapy

J Immune Disord Ther, Volume 02

December 09-10, 2019 | Barcelona, Spain

WORLD CONGRESS ON

IMMUNOLOGY AND CANCER

World Immunology 2019 & Cancer Summit 2019

December 09-10, 2019

Characterisation of clonal and subclonal allelic imbalance at the HLA locus in a 31

patient multi-region profiled primary/metastasis clear cell renal cell carcinoma cohort

Faiz Jabbar

Francis Crick Institute, UK

Introduction

: Metastasis is the primary cause of death in cancer. Large-scale studies of metastatic disease have not included

analysis of matched primary tumours, which are required to distinguish between tumour clones with and without metastatic

potential. Although the treatment of primary tumours has become more successful, five-year survival rates for metastatic renal

cancer remain low at 8%. An improved understanding of the genetic differences between primary and metastatic tumours could

reveal distinct therapeutic vulnerabilities between local and metastatic disease, which if exploited could improve treatment and/

or prevent metastasis. Immune evasion is required for tumors progression and metastasis.

Aims

: We investigated whether genomic alterations causing the loss of Human Leukocyte Antigen (HLA) alleles would facilitate

immune evasion and subsequently promote proliferation and metastasis.

Methods and results

:We acquired the ability to decipher potential modes of metastatic progression through simultaneous analysis

of 418 primary and 278metastatic biopsies from31 renal cell carcinoma patients. Multiple regions from each tumour were biopsied

giving us clonal resolution. AI was investigated using fluorescently labelled STR oligonucleotides that were polymorphic within

the HLA locus. We showed AIHLA was significantly selected for within the metastases. Immunohistochemical analysis on 897

tumour biopsies stained for the proliferation marker Ki67 showed AIHLA did not associate with increased tumour proliferation

rates. The detection of genomic alterations in tumour biopsies is confounded by infiltration from stromal DNA. Therefore, we

developed a novel bioinformatics tool that purified and Characterised Allelic Imbalance in Tumours (CAIT). This was achieved

through mathematical deduction of signals originating from stromal DNA. CAIT increased AIHLA detection, providing insights

on AIHLA’s prevalence and timing.

Discussion

: These results suggest AIHLA could promote metastatic progression. The characterisation of AIHLA could

increase our understanding of drug-resistance mechanisms and inform the development of immunotherapeutic agents targeting

neoantigens.

Biography

Faiz Jabbar studies at University College London as a fifth-year medical student. He has completed a BSc in Immunology, Infection

and Cellular Pathology in 2018, where he investigated the ability of renal cancer to evade the immune system and how it correlated

with metastatic disease, cancer evolution and heterogeneity.