ABFOLFOX (PD-L1 + VEGF + FOLFOX) drives immune-activated CRLM states, with 35% durable control

Atezolizumab (anti–PD-L1) + bevacizumab (anti-VEGF) + leucovorin/5-FU/oxaliplatin (FOLFOX) was evaluated as neoadjuvant therapy for unresectable colorectal liver metastases (CRLM) in a prospectively registered cohort with serial sampling (cohort B, n=20; NCT03698461) alongside a cross-sectional tissue cohort (cohort A, n=60). Durable disease control (PFS≥24 months) occurred in 35% (7/20) on ABFOLFOX; multi-omic profiling suggested stepwise tumor-ecosystem immune remodeling with added agents (notably bevacizumab), with the largest shifts in the ABFOLFOX-treated serial-sampling cohort, and benefit associated with monocyte-lineage programs plus SP140 regulon activation in responders. Stool metagenomics linked higher Prevotella abundance to “good response” and a more immune-active tumor microenvironment, and mediation analysis suggested the gut microbiome partially bridges treatment response and intratumoral immune changes—while clinically, the 24-month disease-control landmark looks meaningfully above typical first-line FOLFOX–bevacizumab median PFS (~9–12 months) reported in mCRC, though the endpoints aren’t directly comparable across designs.