Recent data suggest that patients with colorectal cancer who present with desmoplastic (angiogenic) histopathological growth pattern (HGP) colorectal liver metastases (CLM) might derive more benefit from bevacizumab-based chemotherapy than patients who present with replacement (non-angiogenic) HGP CLM.
The immune phenotype (‘inflamed’, ‘excluded’, ‘desert’) was analyzed regarding the association with HGPs in a cohort of 118 patients with resectable CLM [m:f 66:52, median age 62.3 (31.0-80.4) years, median follow-up 32.2 (5.0-92.7) months] treated with 3 months of neoadjuvant and adjuvant bevacizumab-based chemotherapy and liver resection. The HGPs of CLM were assessed on H&E-stained sections according to international guidelines. The immune phenotypes were based on the distribution pattern of cytotoxic T-lymphocytes in CD8-immunostained tissue sections.
In 39.8% of the lesions the predominant means of vascularization was vessel co-option, as reflected by the replacement HGP. This non-angiogenic growth was associated with worse recurrence-free and overall survival (RFS, OS) with hazard ratios (HR) of 2.03 and 2.63 (P = 0.002 and P = 0.005, respectively). The HGPs were associated with the immune phenotypes. About 60% of the desmoplastic (angiogenic) HGP CLM were ‘inflamed’, while this was true for only 17% of the replacement (non-angiogenic) HGP CLM. More than half of the CLM with non-angiogenic growth were characterized by an immune desert as opposed to only 6% of the angiogenic CLM (P
Immune regulatory and angiogenesis pathways are known to interact. Our data suggest that the inflamed immune phenotype can be induced by systemic treatment in angiogenic CLM. The HGPs therefore are a potential biomarker for treatment that includes targeting the immune contexture.
Clinical trial identification
Legal entity responsible for the study
H-J. Lenz: Consulting or advisory role: Bayer, Novartis, Merck KG, Genentech/Roche, Boehringer-Ingelheim. Research funding: EMD, Bayer, BMS, Genentech/Roche, Merck, Gilead, Medimmune, Array, BostonMedical. All other authors have declared no conflicts of interest.