Comprehensive intrametastatic immune quantification and major impact of immunoscore on survival

Abstract

Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n=441) was performed for two patient cohorts (n=153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI=15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI=4.9 to 30.6; HR=0.45, 95% CI=0.28 to 0.70, P =.02; I 3-4: OS rate = 64.6%, 95% CI=46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI=17.2 to 61.4; HR=0.32, 95% CI=0.15 to 0.66, P =.001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI=14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI =0.8 to 32.4; HR = 0.36, 95% CI =0.22 to 0.57, P