Abstract 575P
Background
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).
Methods
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.
Results
After therapy we observed a decreased CD4/CD8 ratio (P<.0001) and reduced expression levels of CD20 (P<.0001). The expression level of CD3+ and PD-1+ cells after therapy did not change significantly. The relative increase of lymphocytes CD8+ within the CD4/CD8 ratio evaluated on post-operative samples was significantly associated with pathological complete response after CRT (P<.0001), event-free survival (EFS) [hazard ratio (HR)=1.77, 95% confidence interval (CI)=1.08 to 2.89, P=.0227] and overall survival (OS) [HR=2.01, 95% CI=1.19 to 3.4, P=.0087] adjusted for treatment arm and adjuvant chemotherapy.
Conclusions
Our data indicate that CRT may induce an enrichment of CD8+ T lymphocytes and this translates in a better response to CRT and survival. Data on MSI status will be presented at the meeting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University Hospital of Parma.
Funding
SNUPI onlus.
Disclosure
All authors have declared no conflicts of interest.
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