Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2024

In-depth characterisation of the tumour immune microenvironment in paediatric solid cancers – PFA ependymoma and osteosarcoma (#159)

Charlotte Dr Chen 1
  1. Peter MacCallum Cancer Centre, Melbourne, VICTORIA, Australia

The tumour immune microenvironment (TME) provides substantial information on the tumour progression, metastasis which gives insights on the resistance mechanisms to current available immunotherapies [1-4]. At present, paediatric solid tumours pose significant challenges due to the limited understanding of their TME, and thus, unfavourable treatment outcomes with immunotherapies like immune checkpoint blockade (ICB) [5-9]. To advance the development of immunotherapies for paediatric solid tumours, our current studies specifically investigate the TME of two prevalent and challenging cases: posterior fossa A ependymoma (PFA-EPN) and osteosarcoma (OS) with lung metastasis, both associated with dismal survival.

We are conducting retrospective cohort studies comprising 30 patient samples for each disease. In the OS study, we hypothesize the existence of OS-specific immunosuppressive factors in the TME, contributing to lung metastasis. Our goal is to investigate the TME dynamic between the primary tumour and its lung metastasis. In the PFA-EPN study, we hypothesize distinct TME characteristics contributing to the poorest prognosis within paediatric ependymoma.  Our aim is to uncover these features. In both studies, we seek to identify potential treatment resistance mechanisms to ICB by exploring on the TME.

The samples for both studies are sourced from various biobanks within the ANZCHOG, comprising formalin fixed paraffin embedded (FFPE) samples, fresh frozen (FF) samples, and paired frozen PBMCs. Initial profiling involved transcriptomic and genomic analyses of immune subsets and tumour cells. To enhance our insights, we will conduct spatial proteomic and single-cell level transcriptomic analyses on FFPE tissue sections.  Integrating bulk transcriptomic data with spatial analysis will provide a deeper understanding of the interplay between tumour and immune/stromal cells within the TME of individual tumours.

Our current data on PFA-EPN suggested the tumour has “cold” TME with little T cell infiltration, substantial PD-L1+ immunosuppressive myeloid subsets. There is no significant difference in TME profiles between primary and the recurrent tumour. The next step is to conduct single nuclear RNAseq and spatial neighbourhood analysis. We aim to find potential treatment resistance mechanisms through deep interpretation of the interplay between distinct tumour molecular subtypes and the neighbourhood immune subsets. For the OS study, in lung metastasis samples, transcriptomic profiling showed the co-existence of activations on both anti-tumour immunity and myeloid cells mediated immunosuppression. The Spatial analysis of the involved immune subsets and WES analysis are ongoing, which will provide more detailed insights on the mechanisms of metastasis into the lung, and its contribution to treatment resistance.

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