Development of the Peritoneal Metastasis: A Review of Back-Grounds, Mechanisms, Treatments and Prospects

Ren, Kaijie; Xie, Xing; Min, Tianhao; Sun, Tuanhe; Wang, Haonan; Zhang, Yong; Dang, Chengxue; Zhang, Hao

doi:10.3390/jcm12010103

Cited by 15 publications

(6 citation statements)

References 114 publications

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“…This finding may be explained by the greater capability of OC cells to increase their metastatic potential by adhesion to the peritoneum, and survival in a non-permissive TME ( 57 , 58 ). This peritoneal environment provides easy access to adipose tissue modifying cancer cell metabolism, and hypoxic conditions, rendering the TME more complex to achieve antitumoral immunity ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

NLRC5 overexpression in ovarian tumors remodels the tumor microenvironment and increases T-cell reactivity toward autologous tumor-associated antigens

Rodriguez,

Yakubovich,

Murshed

et al. 2024

Front. Immunol.

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IntroductionEpithelial ovarian cancer (OC) stands as one of the deadliest gynecologic malignancies, urgently necessitating novel therapeutic strategies. Approximately 60% of ovarian tumors exhibit reduced expression of major histocompatibility complex class I (MHC I), intensifying immune evasion mechanisms and rendering immunotherapies ineffective. NOD-like receptor CARD domain containing 5 (NLRC5) transcriptionally regulates MHC I genes and many antigen presentation machinery components. We therefore explored the therapeutic potential of NLRC5 in OC.MethodsWe generated OC cells overexpressing NLRC5 to rescue MHC I expression and antigen presentation and then assessed their capability to respond to PD-L1 blockade and an infected cell vaccine.ResultsAnalysis of microarray datasets revealed a correlation between elevated NLRC5 expression and extended survival in OC patients; however, NLRC5 was scarcely detected in the OC tumor microenvironment. OC cells overexpressing NLRC5 exhibited slower tumor growth and resulted in higher recruitment of leukocytes in the TME with lower CD4/CD8 T-cell ratios and increased activation of T cells. Immune cells from peripheral blood, spleen, and ascites from these mice displayed heightened activation and interferon-gamma production when exposed to autologous tumor-associated antigens. Finally, as a proof of concept, NLRC5 overexpression within an infected cell vaccine platform enhanced responses and prolonged survival in comparison with control groups when challenged with parental tumors.DiscussionThese findings provide a compelling rationale for utilizing NLRC5 overexpression in “cold” tumor models to enhance tumor susceptibility to T-cell recognition and elimination by boosting the presentation of endogenous tumor antigens. This approach holds promise for improving antitumoral immune responses in OC.

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Section: Discussionmentioning

confidence: 99%

NLRC5 overexpression in ovarian tumors remodels the tumor microenvironment and increases T-cell reactivity toward autologous tumor-associated antigens

Rodriguez,

Yakubovich,

Murshed

et al. 2024

Front. Immunol.

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“…The development of peritoneal metastases is a multifaceted process, encompassing stages such as the detachment of tumor cells from the primary tumor, their adhesion to the peritoneal surface, subsequent invasion into the submesothelial space, and culminating in tumor growth through angiogenesis 9 , 10 . Notably, immune evasion by disseminated tumor cells within the peritoneal milieu is recognized as a critical event in the progression of PM.…”

Section: Introductionmentioning

confidence: 99%

Vagus nerve signal has an inhibitory influence on the development of peritoneal metastasis in murine gastric cancer

Futoh,

Miyato,

Yamaguchi

et al. 2024

Sci Rep

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The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.

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“…Peritoneal malignancies pose significant clinical challenges due to their poor prognosis [ 1 , 2 , 3 , 4 ]. The peritoneum is a thin layer of squamous mesothelial cells that envelops the organs within the abdominal cavity.…”

Section: Introductionmentioning

confidence: 99%

“…Major subtypes of PPCs include peritoneal mesothelioma, serous carcinomas, desmoplastic small round cell tumors, solitary fibrous tumors, pseudomyxoma peritonei, and primary peritoneal carcinoma of unknown origin. On the other hand, secondary peritoneal cancers (SPCs) or peritoneal carcinomatosis (PC) are more common and arise due to the spread of primary tumors such as colorectal, gastric, pancreatic, ovarian, breast, and lung cancers [ 1 , 4 ]. While primary and secondary peritoneal cancers are different in their origins, studies on SPCs can provide valuable insights into the biology of PPCs.…”

Section: Introductionmentioning

confidence: 99%

Targeting Oncometabolites in Peritoneal Cancers: Preclinical Insights and Therapeutic Strategies

Nadhan

Kashyap

et al. 2023

Metabolites

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Peritoneal cancers present significant clinical challenges with poor prognosis. Understanding the role of cancer cell metabolism and cancer-promoting metabolites in peritoneal cancers can provide new insights into the mechanisms that drive tumor progression and can identify novel therapeutic targets and biomarkers for early detection, prognosis, and treatment response. Cancer cells dynamically reprogram their metabolism to facilitate tumor growth and overcome metabolic stress, with cancer-promoting metabolites such as kynurenines, lactate, and sphingosine-1-phosphate promoting cell proliferation, angiogenesis, and immune evasion. Targeting cancer-promoting metabolites could also lead to the development of effective combinatorial and adjuvant therapies involving metabolic inhibitors for the treatment of peritoneal cancers. With the observed metabolomic heterogeneity in cancer patients, defining peritoneal cancer metabolome and cancer-promoting metabolites holds great promise for improving outcomes for patients with peritoneal tumors and advancing the field of precision cancer medicine. This review provides an overview of the metabolic signatures of peritoneal cancer cells, explores the role of cancer-promoting metabolites as potential therapeutic targets, and discusses the implications for advancing precision cancer medicine in peritoneal cancers.

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Development of the Peritoneal Metastasis: A Review of Back-Grounds, Mechanisms, Treatments and Prospects

Cited by 15 publications

References 114 publications

NLRC5 overexpression in ovarian tumors remodels the tumor microenvironment and increases T-cell reactivity toward autologous tumor-associated antigens

NLRC5 overexpression in ovarian tumors remodels the tumor microenvironment and increases T-cell reactivity toward autologous tumor-associated antigens

Vagus nerve signal has an inhibitory influence on the development of peritoneal metastasis in murine gastric cancer

Targeting Oncometabolites in Peritoneal Cancers: Preclinical Insights and Therapeutic Strategies

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