Abstract
34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 2
Highlights
Cancer cells require outside supply of some non-essential amino acids (NEAAs) to survive
Deprivation of NEAAs could negatively impact the immune activation, an essential process for immunotherapy, because fast cell proliferation poses a higher demand for building blocks such as NEAAs
It is not clear whether dietary NEAA deprivation could be combined with immunotherapy for better safety-efficacy profiles
Summary
Cancer cells require outside supply of some non-essential amino acids (NEAAs) to survive. Immune checkpoint inhibition targeting PD-1/PD-L1 has shown promise in breast cancer but is largely limited to triple negative breast cancer (TNBC).[1] This limitation is primarily due to inherently low levels of tumour infiltrating lymphocytes (TILs), in HR+ disease.[2] Focal radiation therapy (RT) has been shown to generate anti-tumour T cells and increase TILs using mouse models of breast cancer (BC).[3,4] Mechanistically, radiation-induced increase in cytosolic DNA leads to activation of cGAS/STING pathway and production of IFN-훃, which is essential for priming of anti-tumour CD8+ T cells.[5] This process is under the control of TREX1, and dependent on RT dose and fractionation.[5] Inter-tumor variability in optimal RT dose for activating the IFN-I pathway and heterogeneity in immunological response amongst BC subtypes highlight the importance of precision use of RT.[6] We are testing the hypothesis that improved in vitro and in vivo assays allow testing of the pro-immunogenic response to radiation in individual BC patients. In the BALB/c-derived 4T1 mouse model of immunotherapy-refractory metastatic breast cancer, we have previously shown that tumor-targeted radiation therapy (RT) combined with CTLA4 blockade induces CD8+ T cell-mediated regression of irradiated tumors and inhibits lung metastases [2]. We systematically profiled these states across nearly 17,000 solid tumor samples from TCGA, PRECOG [2], in situ transcriptomics arrays, and other publicly available resources, to determined their associations with genomic features, clinical outcomes, and spatial organization
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