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Robotic Duodenum-preserving Total Pancreatic Head Resection for Intraductal Papillary Mucinous Neoplasms

Robotic duodenum-preserving pancreatic head resection (R-DPPHR) is a technically feasible procedure for benign or borderline tumors of the pancreatic ...

Peking Union Medical College, Chinese Academy of Medical Sciences

: C-X-C motif chemokine 5 (CXCL5) is an important attractant for immune cell accumulation in tumor tissues. Recent evidence has shown that CXCL5 could promote carcinogenesis and cancer progression in a variety of cancer types. However, the relationships between CXCL5, immune cell infiltration and pancreatic ductal adenocarcinoma (PDAC) remain largely unknown. This study aimed to explore the role and regulative mechanism of CXCL5 in PDAC carcinogenesis. : The expression of CXCL5 in PDAC was analyzed based on online databases and tissue microarray staining, and Western blotting of CXCL5 in PDAC cell lines and patient samples. The correlation between CXCL5 expression and clinicopathological features, prognosis and immune cell infiltration in tumor tissues was analyzed. : High expression of CXCL5 was observed both in PDAC tumor tissue and PDAC cell lines, compared to normal pancreas tissues and normal ductal epithelium cells. High CXCL5 expression in tumor tissues was positively correlated with an advanced T stage (p=0.036), a positive tumor lymph node metastasis (p=0.014), a poor differentiation status (p=0.003) and a poor prognosis (p=0.001). Combination of CA242 and CXCL5 expression (p<0.0001) served as a better prognostic factor than CA242 alone (p=0.006). In addition, PDAC patients with high CXCL5 expression had more intratumoral M2 polarized macrophages (p=0.0248), neutrophils (p=0.0068) and IgG plasma cells (p=0.0133) than patients with low CXCL5 expression. : The expression of CXCL5 is elevated in pancreatic cancer cells. High CXCL5 expression is positively correlated with poor survival and the increased infiltration of several types of immune suppressive cells. Thus, CXCL5 could be a promising therapeutic target for PDAC immunotherapy.

CXCL5 overexpression predicts a poor prognosis in pancreatic ductal adenocarcinoma and is correlated with immune cell infiltration.

Emerging evidence has shown that intra-tumor immune features are associated with response to immune checkpoint blockade (ICB) therapy. Accordingly, patient stratification is needed for identifying target patients and designing strategies to improve the efficacy of ICB therapy. We aimed to depict the specific immune features of patients with pancreatic cancer and explore the implication of immune diversity in prognostic prediction and individualized immunotherapy.

Immune subtyping for pancreatic cancer with implication in clinical outcomes and improving immunotherapy.

Pancreatic cancer is a highly malignant solid tumor with a poor prognosis and a high mortality rate. Thus, exploring the mechanisms underlying the development and progression of pancreatic cancer is critical for identifying targets for diagnosis and treatment. Two important hallmarks of cancer-metabolic remodeling and epigenetic reprogramming-are interconnected and closely linked to regulate one another, creating a complex interaction landscape that is implicated in tumorigenesis, invasive metastasis, and immune escape. For example, metabolites can be involved in the regulation of epigenetic enzymes as substrates or cofactors, and alterations in epigenetic modifications can in turn regulate the expression of metabolic enzymes. The crosstalk between metabolic remodeling and epigenetic reprogramming in pancreatic cancer has gained considerable attention. Here, we review the emerging data with a focus on the reciprocal regulation of metabolic remodeling and epigenetic reprogramming. We aim to highlight how these mechanisms could be applied to develop better therapeutic strategies.

Crosstalk between metabolic remodeling and epigenetic reprogramming: A new perspective on pancreatic cancer.

Immunoglobulin (Ig) is traditionally believed to be produced solely by B cells. Nonetheless, mounting evidence has demonstrated that various types of Igs are extensively expressed in many cell types. Among them, IgG is found to be highly expressed in cancer cells and is thus labeled as cancer-derived IgG. Cancer-derived IgG shares identical fundamental structures with B cell-derived IgG, but displays several unique characteristics, including restricted variable region sequences and unique glycosylation modifications for those expressed by epithelial cancers. Cancer-derived IgG plays multiple crucial roles in carcinogenesis, including facilitating cancer invasion and metastasis, enhancing cancer stemness, contributing to chemoresistance, and remodeling the tumour microenvironment. Recent studies have discovered that cancer-derived sialylated IgG (SIA-IgG) is extensively expressed in pancreatic cancer cells and is predominantly located in the cytoplasm and on the cell membrane. Cancer-derived IgG expressed by pancreatic cancer presents a restrictive variable region sequence and contains a unique sialylation site of the Fab region. Functionally, cancer-derived IgG participates in pancreatic cancer progression via different mechanisms, such as promoting proliferation, facilitating migration and invasion, resisting apoptosis, inducing inflammation, and modulating the tumour microenvironment. SIA-IgG has shown potential as a clinical biomarker. The expression of SIA-IgG is associated with poor tumour differentiation, metastasis, and chemoresistance in pancreatic cancer. High expression of SIA-IgG can serve as an independent prognostic factor for pancreatic cancer. Additionally, SIA-IgG expression elevated with malignant progression for the precursor lesions of pancreatic cancer. These findings present a prospect of applying cancer-derived IgG as a novel diagnostic and therapeutic target in the management of pancreatic cancer, and aiding in overcoming the challenge in the treatment of this stubborn malignancy.

Cancer-Derived Immunoglobulin G and Pancreatic Cancer.

Intraductal papillary mucinous neoplasm (IPMN) is an important precursor lesion of pancreatic cancer. Systemic inflammatory parameters are widely used in the prognosis prediction of cancer; however, their prognostic implications in IPMN with associated invasive carcinoma (IPMN-INV) are unclear. This study aims to explore the prognostic value of systemic inflammatory parameters in patients with IPMN-INV.

Lymphocyte-to-Monocyte Ratio Predicts Survival for Intraductal Papillary Mucinous Neoplasm with Associated Invasive Carcinoma of the Pancreas: Results from a High-Volume Center.

Tumor microenvironment (TME) can shift towards either immune activation or immunosuppression, influenced by various factors. Recent studies have underscored the pivotal role of sialic acids, a group of monosaccharides with a 9-carbon backbone, in modulating the TME. Aberrant expression or abnormal addition of sialic acids to the surface of cancer cells and within the tumor stroma has been identified as a key contributor to tumor progression. Abnormal sialylation on cancer cell surfaces can inhibit apoptosis, enhance cell proliferation, and facilitate metastasis. Notably, recent findings suggest that dysregulated sialic acid expression in the TME actively contributes to shaping an immunosuppressive niche by reducing the population of anti-tumor immune cells and impairing immune cell function. The mechanisms by which sialic acids foster immune escape and shape the immunosuppressive TME have been partially unraveled, particularly through interactions with sialic acid receptors on immune cells. Importantly, several sialic acid-targeted therapies are currently advancing into clinical trials, offering promising prospects for clinical translation. This dysregulated sialylation represents a significant opportunity for molecular diagnostics and therapeutic interventions in oncology. Targeting aberrant sialylation or disrupting the interaction between sialic acids and their receptors offers potential strategies to reprogram the TME towards an anti-tumor phenotype, thereby facilitating the advancement of innovative cancer therapies.

Sialic Acids: Sweet modulators fueling cancer cells and domesticating the tumor microenvironment.

The advent of the omics era has facilitated the identification of precise biomarkers for cancer progression, revealing a broader diversity of macrophage phenotypes beyond the traditional M1/M2 classification. Folate receptor 2 (FOLR2)-positive macrophages, co-expressing markers such as mannose receptor C-Type 1 (MRC1/CD206) and lymphatic vessel endothelial hyaluronan receptor 1(LYVE1), are an embryonically derived subset typically found around blood vessels in both tumor stroma and normal tissues. Despite FOLR2's longstanding association with anti-inflammatory, immunosuppressive macrophages in tumors, its precise role in cancer progression remains unclear. Recent studies suggest that FOLR2 macrophages can either promote or inhibit cancer progression, depending on their multifaceted roles in the tumor microenvironment. This review provides a comprehensive overview of the biological features, functional roles, molecular mechanisms, and therapeutic potential of FOLR2 macrophages in cancer.

FOLR2 macrophages in cancer: allies or enemies.

Cancer cells orchestrate a highly dynamic and interconnected network spanning metabolic, epigenetic, and immune mechanisms to drive adaptive plasticity and continuous development. This review synthesizes emerging insights into the coevolutionary strategies employed by malignant and stromal cells-particularly tumor cells and immune populations-across the continuum of tumorigenesis, metastasis, and treatment resistance. During tumor initiation, cancer cells rewire metabolism and generate oncometabolites that reshape the chromatin architecture to support immune evasion. Concurrently, metabolic competition in the tumor microenvironment (TME) induces epigenetic exhaustion of cytotoxic T cells, whereas tumor-associated myeloid cells adopt immunosuppressive and angiogenic phenotypes via metabolite-dependent histone modifications to promote carcinogenesis. At metastatic frontiers, under the local metabolic pressure of target organs, tumor cells undergo epigenetic reprogramming to evade immune attacks and support colonization. Premetastatic niches are preconditioned through exosome-mediated transfer of metabolic enzymes and noncoding RNAs that reprogram resident cells before tumor cells arrive. In cancer immunotherapy, tumors often exploit metabolic adaptative strategies to inhibit cell death signaling pathways or the compensatory activation of self-protective mechanisms to circumvent immune-mediated cytotoxicity and develop resistance to immunotherapy. By mapping these dynamic interactions, we propose a novel conceptual framework of the "metabolic-epigenetic-immune axis" that transcends traditional compartmentalized approaches and helps to identify nodal convergence points for therapeutic co-targeting. This review also prioritizes multitarget inhibitors arising from the convergence of metabolic reprogramming, epigenetic plasticity, and immune evasion networks. An integrated approach to these pathways advances next-generation precision oncology strategies aimed at circumventing the evolutionary resilience of cancer.

Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.

The limited effectiveness of T cell-based immune checkpoint blockade (ICB) therapy in most patients with pancreatic ductal adenocarcinoma (PDAC) is largely due to poor CD8 T cell infiltration and a highly immunosuppressive microenvironment driven by excessive myeloid cell accumulation. This highlights the urgent need for new immunotherapy targets and strategies. In this study, an identified pro-cancer factor, cancer cell-derived sialylated IgG (SIA-IgG), is found to be significantly overexpressed in pancreatic cancer cells. SIA-IgG inhibits macrophage phagocytosis and induces an M2-like immunosuppressive phenotype through interactions with Siglec-7/9/10. SIA-IgG and TGF-β1, a key immunosuppressive factor, reinforce each other in a positive feedback loop, promoting immune evasion in PDAC. Blocking SIA-IgG with specific monoclonal antibodies shows significant therapeutic potential through reversal of PDAC's immunosuppressive microenvironment. Our findings identify the SIA-IgG/Siglec axis as an immunotherapeutic target for PDAC, offering a feasible approach for the development of immunotherapeutic strategies.

Cancer cell-derived sialylated IgG interacting with Siglec-7/9/10 is a potential immunotherapeutic target in pancreatic cancer.

Primary hyperparathyroidism (PHPT) is a relatively uncommon endocrine disorder in China. As the national referral center for parathyroid diseases, Peking Union Medical College Hospital (PUMCH) has abundant clinical resources to make parathyroidectomy a valuable surgical procedure for resident training.

Article	Year
CXCL5 overexpression predicts a poor prognosis in pancreatic ductal adenocarcinoma and is correlated with immune cell infiltration. Journal of Cancer\| PubMed ID: 32201508	2020
Immune subtyping for pancreatic cancer with implication in clinical outcomes and improving immunotherapy. Cancer cell international\| PubMed ID: 33637086	2021
Crosstalk between metabolic remodeling and epigenetic reprogramming: A new perspective on pancreatic cancer. Cancer letters\| PubMed ID: 38311052	2024
Cancer-Derived Immunoglobulin G and Pancreatic Cancer. Advances in experimental medicine and biology\| PubMed ID: 38967755	2024
Lymphocyte-to-Monocyte Ratio Predicts Survival for Intraductal Papillary Mucinous Neoplasm with Associated Invasive Carcinoma of the Pancreas: Results from a High-Volume Center. Digestive surgery\| PubMed ID: 38981458	2024
Sialic Acids: Sweet modulators fueling cancer cells and domesticating the tumor microenvironment. Cancer letters\| PubMed ID: 40339953	2025
FOLR2 macrophages in cancer: allies or enemies. Cell communication and signaling : CCS\| PubMed ID: 40457348	2025
Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications. Signal transduction and targeted therapy\| PubMed ID: 41582215	2026
Cancer cell-derived sialylated IgG interacting with Siglec-7/9/10 is a potential immunotherapeutic target in pancreatic cancer. Cell reports. Medicine\| PubMed ID: 41850238	2026
Surgical training program of parathyroidectomy for residents in a national center: a cohort of 122 cases. Surgery in practice and science\| PubMed ID: 41952762	2026

Ming Cui

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