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RT Jacob Stern: One of the most powerful use cases for @sytses' longitudinal single-cell data is in analyzing how his tumor microenvironment evolved i...

Longitudinal single-cell data from Sid's cancer treatment was analyzed using Incytr, revealing neutrophils shifted from receivers to pro-tumor signal senders, resistant to immunotherapy but partially reversed by FAPI radiotherapy. Spatial analysis showed increasing T cell accumulation and oncolytic virus presence in the tumor bed.

Background

- The subject is Sridhar Ramaswamy (@sytses), former Google SVP of Ads, later CEO of Neeva (a search startup). Paul Graham is just re-posting Jacob Stern's thread; Graham is not the patient. - "Longitudinal single-cell data": instead of one biopsy, researchers sequenced individual cells from Ramaswamy's tumor at multiple treatment stages, watching how the tumor's cellular environment evolved. - Key finding: his neutrophils (immune cells) shifted into a pro-tumor "N2 state" that resisted immunotherapy — possibly driven by galectin-1 protein binding to CD45 on immune cells. - FAPI radiotherapy killed FAP+ fibroblasts that were producing galectin-1, which may have broken that pro-tumor signaling loop. - AdAPT-001 is an oncolytic virus (engineered to infect and kill cancer cells); spatial data shows it physically present in the tumor bed. - This is an "N-of-1" precision oncology case: deeply characterizing one patient's data to guide real-time treatment and generate hypotheses for the field.

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