The EACR conference The Tumour Ecosystem: Cellular Interactions and Therapeutic Opportunities was held between 19-21 March 2024 in Bergamo, Italy and brought together 227 delegates from 33 countries.
This EACR conference aimed to explore the dynamics of the tumour microenvironment, in order to achieve a comprehensive, integrated understanding of reciprocal cancer/stroma interactions, and how they are modulated by cancer treatments. To this aim research insights into how the stromal and the immune cells shape the tumour microenvironment, changes in cell metabolism, organ-specific characteristics of the tumour microenvironment and how these novel discoveries could be employed for therapeutic benefit were discussed.
The programme at this conference featured presentations from 14 renowned invited speakers from some of the biggest research institutes in Europe and the US and 8 proffered papers selected from the submitted abstracts. Cutting-edge research was also presented as part of the two poster discussion sessions that featured 134 posters, including 6 Poster Spotlights.
The conference started with an opening keynote lecture from Douglas Hanahan on ‘Immunosuppression in the tumour microenvironment, and beyond’. In his talk, he presented two fascinating research stories from his lab. The first story revealed the involvement of FMRP, an RNA-binding protein known for regulating translation and mRNA in neurons, in orchestrating a multi-faceted anti-tumourigenic immunity response. FMRP regulates expression levels of a network of genes in the tumour microenvironment which modulates the adaptive immune response and contributes to evasion of immune destruction, furthermore, limiting the benefit of immunotherapies [1].
In the second story, Dr. Hanahan presented cutting-edge previously unpublished data building upon his research on the immune-suppressive barriers present in the tumour microenvironment of cervical cancers [2].
Another interesting talk was that of Johanna Joyce who focused her presentation on the complexities of the brain immune microenvironment, discussing how the underlying brain tumour type and genetic profile differentially modulate the tumour microenvironment [3]. Her presentation focused on the immune-suppressive and pro-angiogenic capacity of tumour-associated neutrophils [4] and on the complex interactions that occur between blood vessels, immune cells, and cancer cells [5]. Leila Akkari’s talk also looked at the tumour microenvironment in brain tumours. Building upon her recent research on changes in the glioblastoma immune microenvironment in response to standard therapy [6], Dr. Akkari presented her latest unpublished data on rewiring myeloid cell heterogeneity in cancer.
Further on, Mariia Yuneva’s talk looked at metabolic changes in the context of tumour heterogeneity, with a focus on c-MYC. Dr. Yuneva’s lab used correlative mass spectrometry imaging (MSI) to identify metabolic pathways in breast cancer that could be exploited to identify clinically relevant, tractable metabolic targets for the treatment of cancer [7]. Julio Aguirre-Ghiso also presented some very interesting breast cancer-related data. Dr. Aguirre-Ghiso explored in his talk the relationship between changes that occur over time in the lung microenvironment and the awakening of breast cancer dormant disseminated cells [8].
Another interesting talk was that of Yuval Shaked who discussed host-specific responses to anti-cancer treatment that contribute to therapy resistance. More specifically, Prof. Shaked looked at the impact that chemotherapy and immunotherapy have on the extracellular matrix and how its therapy-induced remodelling impacts the metastatic potential of the tumour [9].
To sum up, The Tumour Ecosystem: Cellular Interactions and Therapeutic Opportunities conference covered the latest exciting breakthroughs in multiple aspects of the tumour microenvironment, including the intricate interactions of cancer cells with the immune system and with specific stromal cells in multiple organs. Novel insights into tumour-host interactions including changes in metabolism, the nervous system and response to therapy were also highlighted.
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References:
- Zeng, Q., et al., Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion. Science, 2022. 378(6621): p. eabl7207.
- Galliverti, G., et al., Myeloid Cells Orchestrate Systemic Immunosuppression, Impairing the Efficacy of Immunotherapy against HPV(+) Cancers. Cancer Immunol Res, 2020. 8(1): p. 131-145.
- Álvarez-Prado Á, F., et al., Immunogenomic analysis of human brain metastases reveals diverse immune landscapes across genetically distinct tumors. Cell Rep Med, 2023. 4(1): p. 100900.
- Maas, R.R., et al., The local microenvironment drives activation of neutrophils in human brain tumors.Cell, 2023. 186(21): p. 4546-4566.e27.
- Bejarano, L., et al., Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms. Cancer Cell, 2024. 42(3): p. 378-395.e10.
- van Hooren, L., et al., CD103+ regulatory T cells underlie resistance to radio-immunotherapy and impair CD8+ T cell activation in glioblastoma. Nature Cancer, 2023. 4(5): p. 665-681.
- Kreuzaler, P., et al., Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer. Nature Metabolism, 2023. 5(11): p. 1870-1886.
- Dalla, E., et al., Tissue-Resident Alveolar Macrophages Control the Timing of Breast Cancer Metastatic Outgrowth in the Lung. Available at SSRN 4453789.
- Haj-Shomaly, J., et al., T Cells Promote Metastasis by Regulating Extracellular Matrix Remodeling following Chemotherapy. Cancer Res, 2022. 82(2): p. 278-291.
