548P - Simplified immune score based on CD8+ T-cells at the invasive margin provides comparable prognostic value to immune scores in non-metastatic colorectal cancer

Background

The Immunoscore® is a validated prognostic stratification tool for colorectal cancer (CRC), yet its adoption is impeded by complex commercial software and patient reimbursement challenges. Utilizing open-source methods, this study aimed to explore whether immune cell scoring can be facilitated by focusing on single T-cell markers, to provide a simplified yet prognostic model in non-metastatic CRC.

Methods

We conducted a multicentric prospective cohort study in non-metastatic CRC patients who underwent curative surgical resection. CD3+ and CD8+ tumor infiltrating lymphocytes [TILs] were quantified in both invasive margin [IM] and tumor core [TC] using QuPath. A composite score, termed immune score (IS), mirroring the methods employed for the Immunoscore®, was calculated based on the TIL densities [CD3IM, CD8IM, CD3TC, CD8TC]. We used a split-sample approach to estimate adjusted hazard ratios of cancer-specific survival [CSS] in a training and a validation set. Classification and regression tree analysis [CART] was performed to select the most prognostic TIL. The model incorporating the CART-selected TIL was compared to a two-tiered IS model for overall performance [Brier score] and discrimination [concordance probability estimate, CPE].

Results

During a median follow-up time of 9.0 years, out of 1260 patients, there were 203 CRC-specific deaths. CART-selected CD8IM was the most prognostic TIL at a cut-off of 231 cells/mm². Patients with CD8IM^Hi had better CSS than CD8IM^Low in both training [HR 0.58, 95% CI 0.40-0.84] and validation sets [HR 0.35, 95% CI 0.21-0.60]. Brier scores of CD8IM and IS survival models were comparable in both training and validation cohort whereas the survival discrimination of CD8IM slightly outperformed the IS in the validation set [CPE: CD8IM 0.748, IS 0.730].

Conclusions

This study found that CD8IM TILs might be a marker as good as the more complex IS for predicting CRC prognosis in non-metastatic CRC patients CD8IM should be further explored as a simple predictive biomarker of adjuvant therapy benefits to advance personalized medicine in early-stage CRC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

German Research Council (HO 5117/2-2).

Disclosure

M. Hoffmeister: Financial Interests, Institutional, Funding, Grant number: HO 5117/2-2: German Research Council. All other authors have declared no conflicts of interest.