575P Impact of immunological alterations and post-operative biomarkers on long-term outcomes in patients with locally advanced rectal cancer: Results from the STAR-01 study cohort

Preoperative chemoradiotherapy (CRT) may enhance antitumor immunity by increasing T-cell activation and tumor infiltration. These effects could possibly sensitize tumour cells to immunecheckpoint inhibitors and other immunotherapies. We investigated the immunologic alterations occurring after preoperative CRT for locally advanced rectal cancer (LARC). The multicenter randomized STAR-01 study compared the preoperative CRT regimen with 50.4 Gy in 28 daily fractions with concomitant infused fluorouracil at the dose of 225 mg/m2/d with the same regimen plus oxaliplatin given weekly at the dose of 60 mg/m2 in patients with LARC. Pre- and/or postoperative specimens were available for 305 patients from this trial (109 paired pre- and post-treatment samples). The immunoistochemical evaluation was performed with a panel of immune cells and associated factors such as CD3, CD20, CD4/CD8, PD-1. The pattern of tumor infiltrating lymphocytes (TILs) and related infiltrating lymphocytes (RILs) were also assessed. Microsatellite instability (MSI)/mismatch repair deficiency (dMMR) was evaluated on pre-treatment tumour biopsies. After therapy we observed a decreased CD4/CD8 ratio (P