Immunity to live: an immunopathoscore using the consensus Immunoscore to best define the risk of recurrence and death in stage IV metastatic patients

Abstract

The consensus Immunoscore is a routine assay quantifying the adaptive immune response within the tumor microenvironment. Its evaluation in the primary tumor of patients with stages I/II/III colorectal cancer (CRC) has prognostic value that has been confirmed in multiple studies. For metastatic patients, the evaluation of the consensus Immunoscore within resected metastases also significantly predicts the recurrence and survival of Stage IV patients. Since recurrence rates post-surgery are still very high, it is important to best evaluate risk parameters using the main patho-molecular and immune parameters. After preoperative treatment and curative resection of 582 metastases from 221 patients, clinico-pathological parameters, RAS mutation, and Immunoscore within metastases were assessed. Immunoscore and clinico-pathological parameters (number of metastases, surgical margin, histopathological growth pattern, and steatohepatitis) were associated with relapse in multivariable analysis. A Pathological Score (PS) that combines relevant clinico-pathological factors for relapse and Immunoscore was significantly (P < .0001) associated with Time to recurrence. In multivariable analysis, only Immunoscore (P < .001) and RAS mutations (P= .03) were prognostic and significantly associated with overall survival. Thus, among all parameters clinically relevant in the metastatic settings, PS and Immunoscore allow the stratification of stage IV CRC patients and identify patients with higher risk of recurrence. Immunoscore remained the major prognostic factor for overall survival (OS). In its latest edition, the WHO classification of Digestive System Tumors introduced for the first time the immune response as an essential and desirable diagnostic criterion for CRC. These novel results highlight the clinical utility of Immunoscore in Stage IV patients.

Keywords: Immunoscore; cancer classification; chemotherapy; immunity; metastasis; pathology; prognosis; stage IV; tumor microenvironment.

Figure 1.

Clinical utility of immunoscore in metastasis. Relative contribution to the risk of death (OS) and Cox multivariateriable analysis for metastatic patients, including the following parameters, size of lesions, number of lesions, surgical margin status (R0/R1), pathological tumor response assessed by tumor regression grading (TRG), histopathological growth pattern (HGP) of liver metastases, molecular status assessed by the presence of BRAF or RAS mutations, chemotherapy-related liver injury (CALI), steatohepatitis, CALI with sinusoidal obstructive syndrome (SOS), CALI with nodular regenerative hyperplasia (NRH), and the consensus immunoscore.