Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Abstract

Background Liver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expression profile of multiple immune cells to further analyze the similarities and differences between the microenvironments of liver metastases and the primary tumor. Methods Tissues from 17 patients with colorectal cancer who underwent resection of primary and liver metastases was analyzed using multispectral immunofluorescence. The expression of multiple immune cells (CD8, Foxp3, CD68, CD163, CD20, CD11c, CD66b, CD56, PD-L1, INF-γ, Ki67 and VEGFR-2) in the tumor center (TC), tumor invasive front (< 150 µm from the tumor center, TF) and peritumoral region (≥ 150 µm from the tumor center, PT) was evaluated via comparison. The expression of CD68 and CD163 in different regions was further analyzed based on the cell colocalization method. In addition, different immune phenotypes were studied and compared according to the degree of CD8 infiltration. Results The expression trends of 12 markers in the TF and TC regions were basically the same in the primary tumor and liver metastasis lesions. However, in comparison of the TF and PT regions, the expression trends were not identical between primary and liver metastases, especially CD163, which was more highly expressed in the PT region relative to the TF region. In the contrast of different space distribution, the expression of CD163 was higher in liver metastases than in the primary foci. Further analysis of CD68 and CD163 via colocalization revealed that the distribution of macrophages in liver metastases was significantly different from that in the primary foci, with CD68−CD163+ macrophages predominating in liver metastases. In addition, among the three immunophenotypes, CD163 expression was highest in the immune rejection phenotype. Conclusions The immune cells found in the primary tumors of colorectal cancer differed from those in liver metastases in terms of their spatial distribution. More immunosuppressive cells were present in the liver metastases, with the most pronounced differential distribution found for macrophages. CD68−CD163+ macrophages may be associated with intrahepatic immunosuppression and weak immunotherapeutic effects.

The analysis of contrast-enhanced ultrasound features of the liver in male patients with liver cancer and unhealthy life habits under 50 years-of-age

“…This is because the blood supply of liver cancer lesions with a high grade of differentiation mainly originates from the portal veins or hepatic arteries; in addition, there is usually a large number of hepatic cell cords and hepatic sinusoids, thus resulting in the slow clearance of contrast agent. In contrast, there are many new vessels and arterial fistulas in liver cancer lesions with a low/ intermediate grade of differentiation, thus resulting in a shorter time to enhancement [30,31]. Thus, physicians can effectively judge the differentiation grades of cancer lesions according to these enhancement features.…”

Construction of a co-expression network and prediction of metastasis markers in colorectal cancer patients with liver metastasis

“…Moreover, the infiltrating immune cells found in the primary tumor of CRC differs from those in liver metastases in terms of their spatial distribution. More immunosuppressive cells are present in the liver metastases, with the most pronounced differential distribution found for macrophages ( 52 ). The infiltrated immune cells in the TME are closely associated with tumorigenesis and metastasis, as well as the cellular response to therapy.…”

N6‐methyladenosine reader hnRNPA2B1 recognizes and stabilizes NEAT1 to confer chemoresistance in gastric cancer

“…mIHC was performed using an Opal 7‐color IHC kit (Akoya Biosciences, Marlborough, MA, USA) as previously described [ 21 ]. First, the slices were baked, dewaxed, rehydrated, and then subjected to antigen retrieval in AR6 (Perkin Elmer, pH = 6.0) or EDTA (50×, pH = 9.0, Proandy, Xi'an, Shaanxi, China) antigen repair solution in a microwave oven for 10 min and then allowed to cool to room temperature.…”