1802MO - Influence of preoperative chemoradiation on tumor-infiltrating lymphocytes in locally advanced rectal cancer: The STAR-01 cohort

Background

Preoperative chemoradiotherapy (CRT) may increase antitumor immunity through enhancing T-cell activation and tumor infiltration. These effects could possibly sensitize tumours to immunotherapies, including checkpoint inhibitors. We explored whether preoperative CRT for locally advanced rectal cancer (LARC) induces immunologic changes and if the post-operative biological parameters are associated with tumour regression grade (TRG sec. Ryan –AJCC Eight ed.).

Methods

The multicenter randomized STAR-01 study compared a standard preoperative CRT regimen (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. Paired pre- and post-operative specimens were available for 81 patients and were analyzed by immunohistochemistry. The immunoistochemical analysis was performed with a panel of immune cells and associated factors as CD3, CD20, CD4/CD8, PD1. The pattern of tumor infiltrating lymphocytes (TILs) and related infiltrating lymphocytes (RILs) was also evaluated. Response to pre-operative chemoradiotherapy was assessed according to TRG.

Results

After therapy we observed a decreased CD4/CD8 ratio (p <0.001) and reduced expression level of CD20 (p<0.001). The expression level of CD3+ and PD-1+ cells after therapy did not change significantly. The relative increase of lymphocytes CD8+ inside CD4/CD8 ratio evaluated on post-operative samples was significantly associated with TRG 0 (p<0.001).

Conclusions

Our data suggest that CRT may induce an enrichment of CD8+ T lymphocytes and this translates in better response to CRT. The new frontier of best treatment could be the use of specific immune cells (T lymphocytes) to trigger the system's immune response against disease.

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.