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New Horizons Across the Immunotherapy Landscape – Lymphoid Structures Drive Immune Checkpoint Therapy and the Efficacy of Cellular Therapeutics

07:56 EST 3 Feb 2020 | SugarCone Biotech

We’d been hearing the rumors for months. But the simultaneous publication in Nature of three papers describing a critical role for lymphoid structures and B cells in supporting T cell anti-tumor immunity was a remarkable milestone in our evolving understanding of immuno-oncology. Really stunning work. Importantly, these papers fit into a new contextual framework and cap a series of studies that have come out over the last year or so that have enriched our understanding of how the immune system and tumor cell populations interact. This broader and still evolving contextual framework will impact immunotherapy drug development across the immune checkpoint field, the tumor vaccine space, innate immune approaches, the T-cell-directed biologics, and cellular therapies. But first, these new papers are gorgeous: The study presented by Petitprez et al. is focused on the response of sarcomas to immunotherapy (https://www.nature.com/articles/s41586-019-1906-8). The soft tissue sarcomas (STS) have mixed clinical responses to immune checkpoint blockade (ICB) treatment, and it is not clear what drives the variable response. In general, STS have been classified as having a low tumor mutational burden (TMB) and are considered non-immunogenic, or ‘cold’, and have little expression of PD-L1. A few STS subtypes are characterized by more complex genetic abnormalities and could potentially have more actionable mutations for the immune system to recognize. Regardless, two of most widely used biomarkers of ICB response (TMB-high or PD-L1-positive) are not generally relevant in STS. In this study, gene expression profiling was used to examine patterns of ICB response in patients across a wide variety of STS subtypes and pathologies. Three distinct genetic classes were identified that match known tumor microenvironments (TME) – immune desert (A), highly vascular (C), and inflamed (E) with two intermediates: B and D. These are well understood classifications and mirror many prior studies of the TME and ICB response and ...

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