Antitumoral immunity in colorectal liver metastases: Histopathological growth patterns and tertiary lymphoid structures

Abstract

Background: Tertiary lymphoid structures (TLSs) and histopathological growth pattern (HGP) are potential prognostic histological features of cancer. We investigated their prognostic value in patients with colorectal cancer liver metastases (CRCLM). Method(s): 133 patients with CRCLM treated by surgical resection from two cancer centres were categorized into desmoplastic (d) and non-desmoplastic (nd) HGP cohorts along with presence/absence of TLS (+/-). Multiplex immunohistochemical staining using 13 immune cell markers was used to determine the cellular composition and spatial distribution of TLSs. Result(s): Patients with CRCLM demonstrating dHGP (n = 54) had improved overall survival compared to patients with ndHGP (n = 79) (Hazard ratio (HR) = 0.53 (0.29-0.93), p = 0.034, log-rank test). Similarly, patients with TLS+ CRCLM (n = 65) showed improved survival compared to those with TLS- CRCLM (n = 68) (HR = 0.51 (0.29-0.90), p = 0.04). On assessment of four patient groups (dHGP/ TLS+ (n = 28), dHGP/ TLS- (n = 26), ndHGP/TLS+ (n = 37), ndHGP/ TLS-(n = 42), there was added prognostic value with absence of both dHGP and TLS having worse prognosis (p = 0.05, chi-square = 7.67, df = 3). Further analysis to interrogate TLS maturation and activity along with spatial distribution is underway to understand their prognostic impact. Conclusion(s): The presence of HGP and TLS individually have prognostic value with added benefit of combining the two parameters. Further evaluation is underway to assess the underlying biological mechanisms.