Immune cellular components and signaling pathways in the tumor microenvironment

Yenyuwadee, Sasitorn; Aliazis, Konstantinos; Wang, Qi; Christofides, Anthos; Shah, Rushil; Patsoukis, Nikolaos; Boussiotis, Vassiliki A.

doi:10.1016/j.semcancer.2022.08.004

Cited by 27 publications

(18 citation statements)

References 275 publications

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“…Tumor-promoting factors in the TME include defective antigen presentation by antigen-presenting cells (APC), mainly dendritic cells (DC), which express inhibitory ligands, upregulation of multiple inhibitory receptors during persistent activation of T cells, such as PD-1, LAG-3, TIGIT, TIM-3, expansion of cell populations that mediate T cell inhibitory functions such as myeloid-derived suppressor cells (MDSCs) and T regulatory (Treg) cells, generation of tumor associated macrophages (TAMs) that lose the ability to phagocytose and present antigens but instead acquire protumorigenic functions, and soluble factors such as IDO, VEGF, and TGF-β, which support cancer cell survival and tumor growth while suppressing the function of immune cells ( 2 ).…”

Section: Cancer Immunosurveillance and Immune Escape In The Tumor Mic...mentioning

confidence: 99%

Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases

Ibis,

Aliazis,

Cao

et al. 2023

Front. Immunol.

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During the past decade, there has been a revolution in cancer therapeutics by the emergence of antibody-based immunotherapies that modulate immune responses against tumors. These therapies have offered treatment options to patients who are no longer responding to classic anti-cancer therapies. By blocking inhibitory signals mediated by surface receptors that are naturally upregulated during activation of antigen-presenting cells (APC) and T cells, predominantly PD-1 and its ligand PD-L1, as well as CTLA-4, such blocking agents have revolutionized cancer treatment. However, breaking these inhibitory signals cannot be selectively targeted to the tumor microenvironment (TME). Since the physiologic role of these inhibitory receptors, known as immune checkpoints (IC) is to maintain peripheral tolerance by preventing the activation of autoreactive immune cells, IC inhibitors (ICI) induce multiple types of immune-related adverse effects (irAEs). These irAEs, together with the natural properties of ICs as gatekeepers of self-tolerance, have precluded the use of ICI in patients with pre-existing autoimmune diseases (ADs). However, currently accumulating data indicates that ICI might be safely administered to such patients. In this review, we discuss mechanisms of well established and newly recognized irAEs and evolving knowledge from the application of ICI therapies in patients with cancer and pre-existing ADs.

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Section: Cancer Immunosurveillance and Immune Escape In The Tumor Mic...mentioning

confidence: 99%

Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases

Ibis,

Aliazis,

Cao

et al. 2023

Front. Immunol.

Self Cite

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“…The composition of immune cells in the tumor microenvironment is an important predictor of bene cial survival and therapeutic outcome [41][42][43]. We found that TFPI2 expression was positively correlated with a variety of immune cells, such as CD8+T cells, B cells, cytotoxic cells and NK cells.…”

Section: Discussionmentioning

confidence: 88%

Low TFPI2 expression is associated with poor prognosis and defective immune cell infiltration in breast cancer disease

Zhu

Dai

Zhang

et al. 2022

Preprint

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Background Breast cancer is the leading cause of death in female cancer population worldwide. The mainstay treatment for breast cancer includes chemotherapy, targeted therapy, endocrine therapy and immunotherapy. Tissue factor pathway inhibitor 2 (TFPI2) plays an important role in balancing the activity of various enzymes in the human environment. However, the correlation of TFPI2 to the prognosis and the immune infiltration in breast cancer has not been reported. Methods We firstly analyzed the expression level of TFPI2 via high-throughput sequencing, clinical sample detection and cancer genome profiling (TCGA). Results TFPI2 expression was significantly downregulated in different subtypes of breast cancer samples. Downregulation of TFPI2 expression was associated with multiple clinical features and poor prognosis. In the tumor microenvironment (TME), TFPI2 is positively correlated with immune cells and immune modulators (chemokines, receptors, immunostimulants, immunosuppressants and MHC). With TFPI2 upregulation, immune and stromal components significantly increased. Conclusion This is the first comprehensive study to reveal that TFPI2 may serve as a novel prognostic biomarker associated with tumor immune infiltration and provide a potential therapeutic target in breast cancer.

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“…We then constructed a logistic model based on DEGs for immunotherapy, which was also verified in the combined ICGC cohort. Notably, the complex interaction between the TME and tumor cells significantly affects immune escape and immunotherapeutic efficacy ( 25 ). Therefore, understanding the TME status and the proportion of immune cell infiltration might contribute to optimizing treatment strategies and assessing tumor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Research into the characteristic molecules significantly affecting liver cancer immunotherapy

et al. 2023

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BackgroundThe past decade has witnessed unprecedented scientific breakthroughs, including immunotherapy, which has great potential in clinical applications for liver cancer.MethodsPublic data were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases and analyzed with R software.ResultsThe LASSO and SVM-RFE machine learning algorithms identified 16 differentially expressed genes (DEGs) related to immunotherapy, namely, GNG8, MYH1, CHRNA3, DPEP1, PRSS35, CKMT1B, CNKSR1, C14orf180, POU3F1, SAG, POU2AF1, IGFBPL1, CDCA7, ZNF492, ZDHHC22, and SFRP2. Moreover, a logistic model (CombinedScore) was established based on these DEGs, showing an excellent prediction performance for liver cancer immunotherapy. Patients with a low CombinedScore might respond better to immunotherapy. Gene Set Enrichment Analysis showed that many metabolism pathways were activated in patients with a high CombinedScore, including butanoate metabolism, bile acid metabolism, fatty acid metabolism, glycine serine and threonine metabolism, and propanoate metabolism. Our comprehensive analysis showed that the CombinedScore was negatively correlated with the levels of most tumor-infiltrating immune cells and the activities of key steps of cancer immunity cycles. Continually, the CombinedScore was negatively associated with the expression of most immune checkpoints and immunotherapy response-related pathways. Moreover, patients with a high and a low CombinedScore exhibited diverse genomic features. Furthermore, we found that CDCA7 was significantly correlated with patient survival. Further analysis showed that CDCA7 was positively associated with M0 macrophages and negatively associated with M2 macrophages, suggesting that CDCA7 could influence the progression of liver cancer cells by affecting macrophage polarization. Next, single-cell analysis showed that CDCA7 was mainly expressed in prolif T cells. Immunohistochemical results confirmed that the staining intensity of CDCA7 was prominently increased in the nucleus in primary liver cancer tissues compared to adjacent non-tumor tissues.ConclusionsOur results provide novel insights into the DEGs and factors affecting liver cancer immunotherapy. Meanwhile, CDCA7 was identified as a potential therapeutic target in this patient population.

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Immune cellular components and signaling pathways in the tumor microenvironment

Cited by 27 publications

References 275 publications

Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases

Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases

Low TFPI2 expression is associated with poor prognosis and defective immune cell infiltration in breast cancer disease

Research into the characteristic molecules significantly affecting liver cancer immunotherapy

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