Principles of risk assessment in colon cancer: immunity is key

ABSTRACT

In clinical practice, the administration of adjuvant chemotherapy (ACT) following tumor surgical resection raises a critical dilemma for stage II colon cancer (CC) patients. The prognostic features used to identify high-risk CC patients rely on the pathological assessment of tumor cells. Currently, these factors are considered for stratifying patients who may benefit from ACT at early CC stages. However, the extent to which these factors predict clinical outcomes (i.e. recurrence, survival) remains highly controversial, also uncertainty persists regarding patients’ response to treatment, necessitating further investigation. Therefore, an imperious need is to explore novel biomarkers that can reliably stratify patients at risk, to optimize adjuvant treatment decisions. Recently, we evaluated the prognostic and predictive value of Immunoscore (IS), an immune digital-pathology assay, in stage II CC patients. IS emerged as the sole significant parameter for predicting disease-free survival (DFS) in high-risk patients. Moreover, IS effectively stratified patients who would benefit most from ACT based on their risk of recurrence, thus predicting their outcomes. Notably, our findings revealed that digital IS outperformed the visual quantitative assessment of the immune response conducted by expert pathologists. The latest edition of the WHO classification for digestive tumor has introduced the evaluation of the immune response, as assessed by IS, as desirable and essential diagnostic criterion. This supports the revision of current cancer guidelines and strongly recommends the implementation of IS into clinical practice as a patient stratification tool, to guide CC treatment decisions. This approach may provide appropriate personalized therapeutic decisions that could critically impact early-stage CC patient care.

KEYWORDS:

• Immunoscore (IS)
• digital pathology
• stage II colon cancer (CC)
• biomarkers
• risk assessment
• high risk
• tumor recurrence
• adjuvant chemotherapy (ACT)
• risk factor
• survival benefit

Disclosure statement

JG has patents associated with the immune prognostic biomarkers and immunotherapies. JG is co-founder of HalioDx biotech company, a Veracyte company and has part-time employment at Veracyte. Immunoscore® a registered trademark from the National Institute of Health and Medical Research (INSERM) licensed to Veracyte.

Additional information

Funding

The work was supported by the Agence Nationale de la Recherche [TERMM ANR-20-CE92-0001]; Institut National de la Santé et de la Recherche Médicale Society for Immunotherapy of Cancer (SITC) Association pour la Recherche contre le Cancer (ARC) Site de Recherche intégrée sur le Cancer (SIRIC) CAncer Research for PErsonalized Medicine [CARPEM, INCa-DGOS-Inserm-ITMO Cancer_18006]; La Ligue contre le Cancer, Institut National du Cancer, France (INCa) Louis Jeantet Prize foundation Assistance publique – Hôpitaux de Paris (AP-HP) HalioDx Transcan ERAnet European project France2030 RHU Remission LabEx Immuno-oncology Qatar National Research Fund [NPRP11S-0121-180351]; Veracyte .