Enrichment of the tumour immune microenvironment in patients with desmoplastic colorectal liver metastasis

Abstract

BACKGROUND: Patients with resected colorectal liver metastasis (CRLM) who display only the desmoplastic histopathological growth pattern (dHGP) exhibit superior survival compared to patients with any non-desmoplastic growth (non-dHGP). The aim of this study was to compare the tumour microenvironment between dHGP and non-dHGP. METHODS: The tumour microenvironment was investigated in three cohorts of chemo-naive patients surgically treated for CRLM. In cohort A semi-quantitative immunohistochemistry was performed, in cohort B intratumoural and peritumoural T cells were counted using immunohistochemistry and digital image analysis, and in cohort C the relative proportions of individual T cell subsets were determined by flow cytometry. RESULTS: One hundred and seventeen, 34, and 79 patients were included in cohorts A, B, and C, with dHGP being observed in 27%, 29%, and 15% of patients, respectively. Cohorts A and B independently demonstrated peritumoural and intratumoural enrichment of cytotoxic CD8+ T cells in dHGP, as well as a higher CD8+/CD4+ ratio (cohort A). Flow cytometric analysis of fresh tumour tissues in cohort C confirmed these results; dHGP was associated with higher CD8+ and lower CD4+ T cell subsets, resulting in a higher CD8+/CD4+ ratio. CONCLUSION: The tumour microenvironment of patients with dHGP is characterised by an increased and distinctly cytotoxic immune infiltrate, providing a potential explanation for their superior survival.

Radiomics and Radiogenomics in Evaluation of Colorectal Cancer Liver Metastasis

“…Evidence has indicated that tumors with limited numbers of infiltrated T cells are in essence frequently resistant to immune therapy (36). Vascular co-opting hepatic lesions of metastasis usually have low infiltration of immune cells or inflammatory cells as demonstrated in lesions with the replacement type of HGP in contrast to those with desmoplastic HGP which are frequently surrounded by a lot of lymphocytes in the dense rime (29,37). Thus, the types of HGPs differentiated using the multidetector CT-based radiomics and MRI-based radiomics (25,30)…”

Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives

“…Interestingly, the distribution of immune cells was different among three HGPs [ 12 ]. Increased cytotoxic CD8 + T cells, CD45 + , CD79A + , Kappa/Lambda, and Self-ligand receptor of the signaling lymphocytic activation molecule family 7 (SLAMF7) + cells and a higher CD8 + /CD4 + ratio were observed in dHGP compared to other HGPs [ 13 , 14 , 15 ]. Additionally, multiple studies showed that desmoplastic type have improved prognosis compared to non-desmoplastic type [ 11 , 13 , 16 , 17 , 18 ].…”

Association between the histopathological growth patterns of liver metastases and survival after hepatic surgery in breast cancer patients

“…For instance, recent reports have suggested that immunotherapy based on checkpoint inhibition is less efficient in metastatic cancer patients with LM 14 . Although more studies are needed to evaluate the immune context in LM, this clinical observation could be related to the fact that LM with the D-HGP generally present the so-called immune-excluded phenotype and LM with the R-HGP the immune-desert phenotype 15 , 16 , as illustrated in Supplementary Fig. 5 .…”