Gene expression profiling of neoadjuvant ABFOLFOX treatment in patients with unresectable colorectal cancer with liver metastases

To characterize the impact of neoadjuvant ABFOLFOX (Atezolizumab, Bevacizumab, and FOLFOX) therapy on the tumor microenvironment of colorectal liver metastases (CRLM), we performed a comprehensive molecular analysis using bulk RNA-seq. The study comprised two distinct cohorts: a cross-sectional cohort (Cohort A, n=60) and a prospective longitudinal cohort (Cohort B, n=20). Cohort A included patients who underwent hepatic surgery, categorized into three groups (n=20 each): those who underwent upfront surgery (G1 group); those treated with neoadjuvant chemotherapy (NAC; FOLFOX or FOLFIRI) (G2 group); and those treated with NAC plus bevacizumab (G3 group). In Cohort B, CRLM specimens were analyzed at three serial time points: T0 (baseline liver biopsy), T1 (biopsy after atezolizumab monotherapy), and T2 (surgical or biopsied specimen after ABFOLFOX). Our findings suggest a progressive increase in immunogenicity within the CRLM tumor ecosystem following treatment. In particular, the monocyte lineage and SP140 regulon appear to serve as potential mediators of the observed therapeutic benefits. This submission presents the transcriptomic data supporting the interplay between systemic therapy and the immune landscape in CRLM.