Adverse effects of low serum lipoprotein cholesterol on the immune microenvironment in gastric cancer: a case‒control study

Zou, Yi; Yu, Xiaoyan; Zhou, Chenqi; Zhu, Chunpeng; Yuan, Ying

doi:10.1186/s12944-022-01766-z

Cited by 4 publications

(2 citation statements)

References 55 publications

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“…The TIME of each tumor was divided into two immune compartments, the TLS zone and the extra-TLS zone, which were assessed independently, as described previously [28]. Briefly, TLS locations were classified into intratumoral (those surrounded by tumor cells), stromal (those surrounded by tumor stromal cells), and peritumoral (those located between tumor and normal tissues) types.…”

Section: Methodsmentioning

confidence: 99%

Correlation of Neuroendocrine Differentiation with a Distinctively Suppressive Immune Microenvironment in Gastric Cancer

Zou,

Li,

et al. 2023

Neuroendocrinology

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Introduction Neuroendocrine neoplasms (NENs) harbored significantly suppressive tumor immune microenvironments (TIMEs). However, the immunological effects of neuroendocrine differentiation (NED) on non-NE neoplasms, such as gastric cancer (GC), were unknown. Methods Between pure gastric cancer (PGC) and GC-NED, TIME features were scored based on expression data and validated on serial whole-tissue sections of surgical samples, with tertiary lymphoid structures (TLSs) and the extra-TLS zone evaluated independently using multi-marker immunohistochemical staining. Risk analyses of TIME features on tumor behaviors were performed in GC-NED. The universal immunological effects of NED were explored preliminarily in adenocarcinomas arising in other organs. Results Based on over 11,500 annotated TLSs and 2,700 extra-TLS zones, compared with PGC, GC-NED harbored a distinctively more suppressive TIME characterized by increased but immature TLSs, with higher naïve B cell and follicular regulatory T cell densities and downregulated TLS maturation-related cell ratios inside TLSs; increased naïve B cell and regulatory T cell densities and a high proportion of exhausted T cells in the extra-TLS zone. The upregulated tumor PD-L1 expression and its close correlations with TLS formation and maturation were remarkable exclusively in GC-NED. TIME features, especially those regarding TLSs, were significantly correlated with tumor growth and invasion. The desynchrony between TLS formation and maturation and increased naïve or regulatory immune cell infiltration was observed in adenocarcinomas of the colorectum, pancreas, lung, and prostate. Conclusion NED highlighted a distinct GC entity with more suppressive TIME features correlated with tumor behaviors, indicating a cohort that would benefit more from immunotherapies.

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Section: Methodsmentioning

confidence: 99%

Correlation of Neuroendocrine Differentiation with a Distinctively Suppressive Immune Microenvironment in Gastric Cancer

Zou,

Li,

et al. 2023

Neuroendocrinology

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“…Recent studies demonstrated that cholesterol served a crucial function in remodeling tumor immune microenvironment ( Figure 2D ). 62 Specifically, the membranal cholesterol level influences T-cell activity and function, 63 and downstream cholesterol products are essential for B-cell migration. 64 A study reported in “Nature” suggested that inhibiting PCSK9, a protein that regulates cholesterol metabolism, could promote tumor response to immune-check-point therapy by enhancing major histocompatibility complex class I protein expression on the surface of tumor cells.…”

Section: Cholesterol-related Tumorigenesis and Progressionmentioning

confidence: 99%

Regulating Cholesterol in Tumorigenesis: A Novel Paradigm for Tumor Nanotherapeutics

Wu,

Zhao

et al. 2024

IJN

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During the past decade, “membrane lipid therapy”, which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of “membrane lipid therapy” for tumors.

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The influence of nutritional status, lipid profile, leptin concentration and polymorphism of genes encoding leptin and neuropeptide Y on the effectiveness of immunotherapy in advanced NSCLC patients

Frąk,

Grenda,

Krawczyk

et al. 2024

BMC Cancer

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Introduction Neuropeptide Y is a neurotransmitter in the nervous system and belongs to the orexigenic system that increases appetite. Its excessive secretion leads to obesity. Leptin is a pro-inflammatory adipokine (produced in adipose tissue) induced in obesity and may mediate increased antitumor immunity in obesity (including the promotion of M1 macrophages). Leptin and neuropeptide Y gene polymorphisms, causing increased leptin levels and the occurrence of obesity, and lipid profile disorders, may increase the effectiveness of immunotherapy. Materials and methods In 121 patients with advanced NSCLC without mutations in the EGFR gene and rearrangements of the ALK and ROS1 genes, undergoing immunotherapy (1st and 2nd line of treatment) or chemoimmunotherapy (1st line of treatment), we assessed BMI, lipid profile, PD-L1 expression on cancer cells using the immunohistochemical method (clone SP263 antibody), leptin concentration in blood serum by ELISA, polymorphisms in the promoter region of the genes for leptin ( LEP ) and neuropeptide Y ( NPY ) by real-time PCR. Results Leptin concentration was significantly higher in obese patients than in patients with normal or low weight ( p = 0.00003) and in patients with disease stabilization compared to patients with progression observed during immunotherapy ( p = 0.012). Disease control occurred significantly more often in patients with the GA or AA genotype than patients with the GG genotype in the rs779039 polymorphism of the LEP gene. The median PFS in the entire study group was five months (95% CI: 3-5.5), and the median OS was 12 months (95% CI: 8–16). Median PFS was highest in patients with TPS ≥ 50% (6.5 months) and in obese patients (6.6 months). Obese patients also had a slightly longer median OS compared to other patients (23.8 vs. 13 months). The multivariate Cox logistic regression test showed that the only factor reducing the risk of progression was TPS ≥ 50% (HR = 0.6068, 95% CI: 0.4001–0.9204, p = 0, 0187), and the only factor reducing the risk of death was high leptin concentration (HR = 0.6743, 95% CI: 0.4243–1.0715, p = 0.0953). Conclusion Assessment of nutritional status, serum leptin concentration and polymorphisms in the LEP gene may be of additional importance in predicting the effectiveness of immunotherapy and chemoimmunotherapy in patients with advanced NSCLC.

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Adverse effects of low serum lipoprotein cholesterol on the immune microenvironment in gastric cancer: a case‒control study

Cited by 4 publications

References 55 publications

Correlation of Neuroendocrine Differentiation with a Distinctively Suppressive Immune Microenvironment in Gastric Cancer

Correlation of Neuroendocrine Differentiation with a Distinctively Suppressive Immune Microenvironment in Gastric Cancer

Regulating Cholesterol in Tumorigenesis: A Novel Paradigm for Tumor Nanotherapeutics

The influence of nutritional status, lipid profile, leptin concentration and polymorphism of genes encoding leptin and neuropeptide Y on the effectiveness of immunotherapy in advanced NSCLC patients

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