WEHI Wednesday Seminar hosted by Professor Marie-Liesse Labat

Dr Adithya Balasubramanian
PhD Student – Labat Lab, Personalised Oncology division – Cancer Research & Treatments Theme, WEHI
(this is a PhD Completion seminar)

Targeting tumour cell-specific MHC regulators to enhance anti-tumour immunity in lung adenocarcinoma

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

The advent of immune checkpoint inhibitors (ICIs) have heralded the potential for long term survival in patients with lung adenocarcinoma (LUAD)- the most common subtype of lung cancer. However, the majority do not respond and this condition remains the leading cause of cancer related death in Australia. In particular, ‘never smoker’ (NS) patients with LUAD derive inferior benefit from ICI treatment compared to those with a smoking history (‘ever smokers’ [ES]). There is an unmet need to improve outcomes in both populations.

Escaping immune destruction is one of the hallmarks of cancer. One such immune evasion mechanism deployed by tumour cells is to reduce neoantigen presentation through silencing of the antigen presentation machinery (APM). Major histocompatibility complex class I (MHC-I) loss is a well characterised means of immune escape. However other underexplored mechanisms of APM silencing exist with more favourable characteristics to be exploited as therapeutic targets. Tumour specific MHC-II (tsMHC-II) is recognised as a prognostic and predictive cancer biomarker. Its regulation may be independent of MHC-I and it binds greater diversity of neoantigens.

Using in vitro pooled CRISPR Cas9 screens, Adi’s PhD project has identified a unique regulator of tsMHC-II expression in NS LUAD and ubiquitous regulator of tsMHC-I in both NS and ES LUAD. In this seminar, Adi will outline his screen design, the discovery of regulators of MHC-II and validation of their clinical significance through clinical cohort patient data analysis and functional assays.

All welcome!