Systemic and local inflammation in colorectal cancer

Rumba, Roberts; Cipkina, Sandra; Cukure, Fanija; Vanags, Andrejs

doi:10.6001/actamedica.v25i4.3929

Cited by 16 publications

(12 citation statements)

References 57 publications

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“…Local inflammation appears to be reflected at the systemic level, and this is supported by several studies ( 6 , 206 , 207 ). Routine hematological parameters have been used in recent years as indicators of systemic inflammation.…”

Section: Parameters To Assess Systemic Immune-inflammatory Markerssupporting

confidence: 61%

The systemic-level repercussions of cancer-associated inflammation mediators produced in the tumor microenvironment

et al. 2022

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The tumor microenvironment is a dynamic, complex, and redundant network of interactions between tumor, immune, and stromal cells. In this intricate environment, cells communicate through membrane–membrane, ligand–receptor, exosome, soluble factors, and transporter interactions that govern cell fate. These interactions activate the diverse and superfluous signaling pathways involved in tumor promotion and progression and induce subtle changes in the functional activity of infiltrating immune cells.The immune response participates as a selective pressure in tumor development. In the early stages of tumor development, the immune response exerts anti-tumor activity, whereas during the advanced stages, the tumor establishes mechanisms to evade the immune response, eliciting a chronic inflammation process that shows a pro-tumor effect.The deregulated inflammatory state, in addition to acting locally, also triggers systemic inflammation that has repercussions in various organs and tissues that are distant from the tumor site, causing the emergence of various symptoms designated as paraneoplastic syndromes, which compromise the response to treatment, quality of life, and survival of cancer patients. Considering the tumor–host relationship as an integral and dynamic biological system, the chronic inflammation generated by the tumor is a communication mechanism among tissues and organs that is primarily orchestrated through different signals, such as cytokines, chemokines, growth factors, and exosomes, to provide the tumor with energetic components that allow it to continue proliferating. In this review, we aim to provide a succinct overview of the involvement of cancer-related inflammation at the local and systemic level throughout tumor development and the emergence of some paraneoplastic syndromes and their main clinical manifestations. In addition, the involvement of these signals throughout tumor development will be discussed based on the physiological/biological activities of innate and adaptive immune cells. These cellular interactions require a metabolic reprogramming program for the full activation of the various cells; thus, these requirements and the by-products released into the microenvironment will be considered. In addition, the systemic impact of cancer-related proinflammatory cytokines on the liver—as a critical organ that produces the leading inflammatory markers described to date—will be summarized. Finally, the contribution of cancer-related inflammation to the development of two paraneoplastic syndromes, myelopoiesis and cachexia, will be discussed.

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Section: Parameters To Assess Systemic Immune-inflammatory Markerssupporting

confidence: 61%

The systemic-level repercussions of cancer-associated inflammation mediators produced in the tumor microenvironment

et al. 2022

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“…Thus, a chronic inflammatory state, inter alia mediated by an up-or downregulation of TLRs, is closely related to the development of CRC (Pretzsch et al 2019;Fukata et al 2007). However, only little is known about the influence of immunological processes on the development of distant metastases (Rumba et al 2018). In this respect, the present analysis demonstrated a significant overrepresentation of an immunological gene set consisting of 17 genes.…”

Section: Hep Vs M0: Reactome Toll-like Receptor-cascadementioning

confidence: 49%

The association of immunosurveillance and distant metastases in colorectal cancer

Jacob

Jurinović

Lampert

et al. 2021

J Cancer Res Clin Oncol

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Background Colorectal cancer (CRC) is the third most common malignancy worldwide, but the key driver to distant metastases is still unknown. This study aimed to elucidate the link between immunosurveillance and organotropism of metastases in CRC by evaluating different gene signatures and pathways. Material and methods CRC patients undergoing surgery at the Department of General, Visceral and Transplantation Surgery at the Ludwig-Maximilian University Hospital Munich (Munich, Germany) were screened and categorized into M0 (no distant metastases), HEP (liver metastases) and PER (peritoneal carcinomatosis) after a 5-year follow-up. Six patients of each group were randomly selected to conduct a NanoString analysis, which includes 770 genes. Subsequently, all genes were further analyzed by gene set enrichment analysis (GSEA) based on seven main cancer-associated databases. Results Comparing HEP vs. M0, the gene set associated with the Toll-like receptor (TLR) cascade defined by the Reactome database was significantly overrepresented in HEP. HSP90B1, MAPKAPK3, PPP2CB, PPP2R1A were identified as the core enrichment genes. The immunologic signature pathway GSE6875_TCONV_VS_FOXP3_KO_TREG_DN with FOXP3 as downstream target was significantly overexpressed in M0. RB1, TMEM 100, CFP, ZKSCAN5, DDX50 were the core enrichment genes. Comparing PER vs. M0 no significantly differentially expressed gene signatures were identified. Conclusion Chronic inflammation might enhance local tumor growth. This is the first study identifying immune related gene sets differentially expressed between patients with either liver or peritoneal metastases. The present findings suggest that the formation of liver metastases might be associated with TLR-associated pathways. In M0, a high expression of FOXP3 + tumor infiltrating lymphocytes (TILs) seemed to prevent at least in part metastases. Thus, these correlative findings lay the cornerstone to further studies elucidating the underlying mechanisms of organotropism of metastases.

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Section: Cytokines and Chemokines Induce Inflammation In Crcmentioning

confidence: 99%

“…Although intense local inflammation is associated with antitumor immune responses, systemic inflammation is associated with protumor immune response, poor prognosis [ 75 ], and reduced OS in advanced CRC [ 76 , 77 , 78 ]. Systemic inflammation elicits a favorable TME for tumor initiation and progression, angiogenesis, increased vascular permeability, cancer cell infiltration [ 75 ], and PMN development, thereby promoting distant metastases [ 79 ]. Although the major driving factors of systemic inflammation responses are complicated and elusive [ 80 ], its hallmarks in CRC include elevated proinflammatory cytokines and acute‐phase proteins that enter the blood circulation [ 16 ].…”

Section: Cytokines and Chemokines Induce Inflammation In Crcmentioning

confidence: 99%

Cytokine‐ and chemokine‐induced inflammatory colorectal tumor microenvironment: Emerging avenue for targeted therapy

Bhat

Nisar

Singh

et al. 2022

Cancer Communications

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Colorectal cancer (CRC) is a predominant life‐threatening cancer, with liver and peritoneal metastases as the primary causes of death. Intestinal inflammation, a known CRC risk factor, nurtures a local inflammatory environment enriched with tumor cells, endothelial cells, immune cells, cancer‐associated fibroblasts, immunosuppressive cells, and secretory growth factors. The complex interactions of aberrantly expressed cytokines, chemokines, growth factors, and matrix‐remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes. Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment, which is partly achieved by the recruitment of immunosuppressive cells. These cells impart features such as cancer stem cell‐like properties, drug resistance, invasion, and formation of the premetastatic niche in distant organs, promoting metastasis and aggressive CRC growth. A deeper understanding of the cytokine‐ and chemokine‐mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC. Here, we summarized the current knowledge of cytokine‐ and chemokine‐mediated crosstalk in the inflammatory tumor microenvironment, which drives immunosuppression, resistance to therapeutics, and metastasis during CRC progression. We also outlined the potential of this crosstalk as a novel therapeutic target for CRC. The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review.

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Systemic and local inflammation in colorectal cancer

Cited by 16 publications

References 57 publications

The systemic-level repercussions of cancer-associated inflammation mediators produced in the tumor microenvironment

The systemic-level repercussions of cancer-associated inflammation mediators produced in the tumor microenvironment

The association of immunosurveillance and distant metastases in colorectal cancer

Cytokine‐ and chemokine‐induced inflammatory colorectal tumor microenvironment: Emerging avenue for targeted therapy

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