Characterization of the immunoscore of synchronous resected primary tumor and liver colorectal cancer metastases

Abstract

Background: Pooled analysis from previous trials including unresectable metastatic colorectal cancer (mCRC) patients suggests an independent survival benefit of palliative primary tumor resection. Regarding the reported prognostic survival impact of Immunoscore (I) after resection of primary colorectal tumor (PCT) and liver colorectal metastases (LCM), we investigate if (I) could be different in PCT compared to LCM in a subgroup of synchronously resected mCRC patients. Methods: From a cohort of mCRC patients undergoing curative LCM resection, patients with synchronous resection of LCM and PCT were analyzed. The density of CD3 (T cells) and CD8 (cytotoxic) in the core (CT) and invasive margin (IM) of all synchronous LCM and PCT was quantified with a dedicated image analysis software and used to calculate the CD3/CD8 Immunoscore (I) range from 0 (I0), when low densities of both cell types are found in the CT and IM of the tumor, to 4 (I4) when high densities for both markers are found in both regions. The (I) of the PCT, the mean value of all LCM, the least and the most infiltrated LCM per patient were analyzed and compared using the Fisher's exact test. Results: Among 161 patients with curative resection of LCM (n = 459), 29 patients (M : 14, F :15 : mean 62,9 y-old) had synchronous LCM (n = 68, mean :2,34/pt) and PCT (n = 29) resection after preoperative treatment (n = 14) or not (n = 15). Low (I) I0-1-2 is significantly associated with PCT compared to the mean of all, the least and the most infiltrated LCM per patient (p < 0,0002). PCT had low proportion of I3-4 (13,8%) compared to the least (41,4%, p = 0,04), the mean of all (62,1%, p = 0,0003) and the most infiltrated LCM per patient (65,5% p = 0,0001). This was not confirmed for patients with metachronous metastases (n = 15). Conclusions: In patients with synchronously resected PCT and LCM, PCT was significantly associated with a low Immunoscore compared to the LCM. This result would suggest that mCRC patients would indeed benefit from the removal of their low infiltrated PCTs, potential source of future metastases.