Prognostic and predictive value of Immunoscore and its correlation with ctDNA in stage II colorectal cancer

ABSTRACT

This study aimed to validate the prognostic value of Immunoscore (IS) in stage II colorectal cancer (CRC), and explore the roles of IS and circulating tumor DNA (ctDNA) in the adjuvant treatment for early-stage CRC. Resected tumor samples from stage II CRC patients were collected from the Sun Yat-sen University Cancer Center. The densities of CD3+ and CD8+ lymphocytes were quantified and converted to IS and classified into Low, Intermediate (Int), and High groups according to predefined cutoffs. A total of 113 patients were included in the study. Patients with IS-High, Int, and Low were 43 (38%), 62 (55%), and 8 (7%), respectively. Patients with IS-High had an excellent clinical outcome, with none recurring during a median follow-up of 3 years, including 15 (35%) clinical high-risk patients. The 3-year disease-free survival (DFS) was 100% for IS-High, 76% for IS-Int, and 47% for IS-Low (P < .001). In the multivariate Cox analysis, IS was the only significant parameter associated with DFS. IS-Int and IS-Low patients with adjuvant chemotherapy had improved DFS compared to those who did not receive adjuvant chemotherapy (HR = 0.3; 95% CI 0.1–0.92; P = .026). Among the 49 patients with postoperative ctDNA data, IS-High patients had the lowest ctDNA positivity rate, suggesting that they were most eligible for chemotherapy-free treatment. IS had a strong prognostic value in Chinese patients with stage II CRC and demonstrates its clinical utility. IS and ctDNA will jointly optimize the adjuvant treatment strategies for early-stage CRC.

KEYWORDS:

• Immunoscore
• colorectal cancer
• prognostic
• predictive
• adjuvant chemotherapy
• ctDNA

Highlights

• Immunoscore (IS) is a strong prognostic biomarker for Chinese stage II colorectal cancer patients.

• Patients with high IS had a 100% DFS rate during a median follow-up of 3 years

• Patients with intermediate to low IS could significantly benefit from adjuvant chemotherapy demonstrating IS clinical utility

• IS and postoperative ctDNA will jointly optimize the adjuvant treatment strategy for stage II colon cancer.

Acknowledgments

The authors are very grateful to all the participants and their families.

List of abbreviations

IS	=	Immunoscore
CRC	=	Colorectal cancer
CC	=	Colon cancer
Int	=	Intermediate
DFS	=	Disease-free survival
ctDNA	=	Circulating tumor DNA
SITC	=	Society for Immunotherapy of Cancer
SYSUCC	=	Sun Yat-sen University Cancer Center
CAPOX	=	Capecitabine plus oxaliplatin
CEA	=	carcinoembryonic antigen
chemo	=	chemotherapy
Hi	=	high
Int	=	intermediate
pMMR	=	Proficient mismatch-repair
VELIPI	=	Vascular, lymphatic, or perineural invasion
dMMR	=	Mismatch-repair deficiency
Mod/Well	=	moderate or well
RMST	=	Restricted mean survival time
IQR	=	Interquartile range
HR	=	Hazard ratio
MRD	=	Minimal residual disease
ACT	=	adjuvant chemotherapy

Disclosure statement

JQ is employed by Genecast Biotechnology Co., Ltd. AC and JG are employed by Veracyte company. JG has a patent for Immunoscore and is a co-founder of HalioDx, now Veracyte. Immunoscore® is a registered trademark from the National Institute of Health and Medical Research (INSERM) licensed to HalioDx. All remaining authors have declared no conflicts of interest.

Data availability statement

The data presented in this study are available on request from the corresponding author (http://www.ici.upmc.fr/contact.shtml).

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Sun Yat-sen University Cancer Center (approval number: B2020-178-01).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2022.2161167

Additional information

Funding

This research received no external funding.