The Scavenger Receptor MARCO Expressed by Tumor-Associated Macrophages Are Highly Associated With Poor Pancreatic Cancer Prognosis

Abstract

Macrophage-targeting therapies have become attractive strategies for immunotherapy. Deficiency of MARCO significantly inhibits tumor progression and metastasis in murine models of pancreatic cancer. However, the role of MARCO in patients with pancreatic cancer remains unclear. In the present study, we analyzed tumor-associated macrophage (TAM)-related changes using the Cancer Genome Atlas database. We observed a significant enrichment of M2 macrophages in pancreatic cancer tissues. We found that several pro-tumor markers are increased in cancer tissues, including CD163, CD206, SIRPα, LILRB1, SIGLEC10, AXL, MERTK, and MARCO. Crucially, MARCO is highly or exclusively expressed in pancreatic cancer across many types of solid tumors, suggesting its significant role in pancreatic cancer. Next, we investigated the expression of MARCO in relation to the macrophage marker CD163 in a treatment-naïve pancreatic cancer cohort after surgery (n = 65). MARCO and CD163 were analyzed using immunohistochemistry. We observed increased expression of CD163 and MARCO in pancreatic cancer tissues compared with paracancerous tissues. Furthermore, we observed a large variation in CD163 and MARCO expression in pancreatic cancer tissues among cases, suggesting the heterogeneous expression of these two markers among patients. Correlation to clinical data indicated a strong trend toward worse survival for patients with high CD163 and MARCO macrophage infiltration. Moreover, high CD163 and MARCO expression negatively affected the disease-free survival and overall survival rates of patients with pancreatic cancer. Univariate and multivariate analysis revealed that CD163 and MARCO expression was an independent indicator of pancreatic cancer prognosis. In conclusion, high CD163 and MARCO expression in cancer tissues is a negative prognostic marker for pancreatic cancer after surgery. Furthermore, anti-MARCO may be a novel therapy that is worth studying in depth.

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma

“…Follow-up and survival analysis of ICC Patients were consistent with previous studies [ 13 , 35 ]. After surgery, the patients were checked regularly.…”

“…If follow-up evaluations revealed metastatic disease and/or local recurrences, other therapies were applied, including conventional therapies (surgery, chemotherapy, and radiotherapy) as well as targeted and immunotherapy. Disease-free survival (DFS) was calculated from the date of surgery to the time of recurrence or metastasis, and patients who were alive and in a stable state were censored at the time of last contact [ 13 , 35 ]. Overall survival (OS) was calculated using the date of surgery to the time of death, and patients who were alive at the time of last contact were censored [ 13 , 35 ].…”

“…Disease-free survival (DFS) was calculated from the date of surgery to the time of recurrence or metastasis, and patients who were alive and in a stable state were censored at the time of last contact [ 13 , 35 ]. Overall survival (OS) was calculated using the date of surgery to the time of death, and patients who were alive at the time of last contact were censored [ 13 , 35 ]. DFS and OS were calculated using the Kaplan–Meier analysis.…”

“…Clinical studies and experimental mouse models suggest that these macrophages often play a pro-tumoral role [ 8 ]. Several markers of TAMs such as CD206 [ 9 ], CD163 [ 10 ], ARG1 [ 11 ], and MARCO [ 12 , 13 ] have been significantly correlated with aggressive tumor phenotypes and worse prognosis in tumors. In recent years, many studies have revealed that tumor cells evade phagocytosis by TAMs through high expression of phagocytosis checkpoints.…”

Deciphering the heterogeneous niche in the tumor progression of hepatocellular carcinoma: a Spatial single-cell landscape and multi-omics atlas analysis

“…Interestingly, we found that CCL2, IL1B, and MARCO were remarkably expressed in the Kupffer cell subpopulation. Previous studies have confirmed that higher MARCO expression is associated with poor prognosis in a variety of cancers [50-52] . More importantly, preclinical studies have shown that anti-MARCO antibodies inhibit tumor growth and metastasis in 4T1 breast cancer and B16 melanoma mouse models [53] .…”