Abstract:
: Background : Peritoneal carcinomatosis (PC) is a terminal evolution from primary colorectal cancer (pCRC) associated with poor patient survival. Impact of the immune cell infiltrate on PC pathogenesis is unknown. Therefore, we characterized the immunological tumor microenvironment regarding proliferation, senescence and neovascularization. Methods : Formalin-fixed and paraffin-embedded (FFPE) tissue of PC and pCRC was examined by immunohistochemistry. Cells infiltrating resected tissue were isolated and analyzed by flow cytometry. PCR arrays detected the expression of genes relevant for helper T (TH) cell responses, like TH1, TH2 and TH17 response. Results : PC tumor cells demonstrate significantly lower proliferation rates than pCRC, but show significantly more senescence. PC is surrounded by significantly increased numbers of cytotoxic active Natural Killer (NK) cells, follicular helper T cells (TFH) and B cells, whereas pCRC shows more CD4+ TH cells, CD8+ cytotoxic T (TC) cells, eosinophilic granulocytes, TH17 and regulatory T (Treg) cells. PC is characterized by significantly increased interferon-γ (IFNγ), an upregulation of tumor necrosis factor (TNF) and the NK cell-regulating cytokine interleukin-15 (IL-15). An upregulation of angiogenesis-related genes, like vascular endothelial growth factor-A (VEGF-A), leads to severe neovascularization in PC. Correlations of PC results reveal that elevated numbers of interleukin-17 (IL-17) positive cells are associated with high cancer cell proliferation, whereas high numbers of IFNγ positive cells correlate with more tumor cells in senescence. Conclusion : The cellular immune reaction is modified during metastasis, inducing senescence in PC tumor cells. Immune surveillance in PC is facilitated by NK cells and high levels of IFNγ and TNF. Counteracting this effect, TFH and B cells combined with VEGF-A enhancement promote neovascularization in PC (Illustration 1). During metastasis from primary CRC to PC the immune cell infiltrate changes, accompanied by the induction of senescence in PC cancer cells (marked red): In pCRC, the antitumor immune response is facilitated by CD4+TH cells, CD8+TC cells and PRG2+ eosinophilic granulocytes. The premetastatic niche development is promoted by Treg cells and TH17 cells producing systemic factors like VEGF-A, TGF-β and TNF. Along with TFH and B cells, as with a pro-tumor immune response, they support metastatic formation and lead to severe neovascularization in PC. This is counterbalanced by the IL-15-induced activation and proliferation of NK cells. The secreted cytokines IFNγ and TNF mediate immunosurveillance.
journal_name
Oncoimmunologyjournal_title
Oncoimmunologyauthors
Seebauer CT,Brunner S,Glockzin G,Piso P,Ruemmele P,Schlitt HJ,Geissler EK,Fichtner-Feigl S,Kesselring Rdoi
10.1080/2162402X.2016.1242543subject
Has Abstractpub_date
2016-10-14 00:00:00pages
e1242543issue
12eissn
2162-4011issn
2162-402Xpii
1242543journal_volume
5pub_type
杂志文章相关文献
OncoImmunology文献大全abstract::The comprehensive analysis of patients with a complete resection of all metastases reveals the heterogeneity of the colorectal metastatic disease and its clinical impact. Complex tumor immune interrelations shape the metastatic landscape, not only in terms of number and size of lesions, or mutational pattern, but also...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2020.1824316
更新日期:2020-09-29 00:00:00
abstract::A substantial obstacle to the success of adoptive T cell-based cancer immunotherapy is the sub-optimal affinity of T-cell receptors (TCRs) for most tumor antigens. Genetically engineered TCRs that have enhanced affinity for specific tumor peptide-MHC complexes may overcome this barrier. However, this enhancement risks...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2019.1682381
更新日期:2019-11-24 00:00:00
abstract::Adoptive cell transfer immunotherapy against melanoma is highly effective. However, this therapy has seen limited dissemination, mainly due to the complexity and costs of cell expansion protocols. Two bioreactors have recently been described that simplify and streamline the production of individualized cell therapies....
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.21206
更新日期:2012-11-01 00:00:00
abstract::Cancer immunotherapy is hampered by the immunosuppression maintained by regulatory T cells (Tregs) in tumor-bearing hosts. Stimulation of the Toll-like receptor 2 (TLR2) by Pam3Cys is known to affect Treg-mediated suppression. We found that Pam3Cys increases the proliferation of both CD4(+) effector T cells (Teffs) an...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.21479
更新日期:2012-11-01 00:00:00
abstract::In the context of a Phase I clinical trial, the long-term vaccination of advanced biliary tract cancer patients with peptides derived from four distinct cancer-testis antigens resulted in remarkable disease stability and in the elicitation of antigen-specific T-cell responses. ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.24882
更新日期:2013-07-01 00:00:00
abstract::Vaccines in combination with chemotherapy have been shown to be safe in different tumor types. We investigated the immunological activity of the TroVax® vaccine in combination with pemetrexed-cisplatin chemotherapy in malignant pleural mesothelioma (MPM). In this first line, open-label, single-arm, phase 2 study, pati...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1457597
更新日期:2018-09-07 00:00:00
abstract::Type I interferon (IFN) release by irradiated cancer cells is paramount for radiation therapy to elicit anticancer immunity. Our findings demonstrate that mitochondrial outer membrane permeabilization (MOMP) triggered by RT enables exposure of mitochondrial DNA to the cytosol, hence setting off CGAS-driven type I IFN ...
journal_title:Oncoimmunology
pub_type: 社论
doi:10.1080/2162402X.2020.1797292
更新日期:2020-07-22 00:00:00
abstract::We previously showed that the colorectal cancer colonizing bacterium Fusobacterium nucleatum protects tumors from immune cell attack via binding of the fusbacterial Fap2 outer-membrane protein to TIGIT, a checkpoint inhibitory receptor expressed on T cells and NK cells. Helicobacter pylori, the causative agent for pep...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1553487
更新日期:2019-01-29 00:00:00
abstract::The achievement of malignant traits in several cancers is associated with tumor microenvironment reactivity. New evidence show that the stress hormone noradrenaline enhances melanoma microenvironment reactivity, mainly acting through β3-adrenoreceptors (β2-ARs), favoring recruitment of cancer-associated fibroblasts, M...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1026532
更新日期:2015-04-02 00:00:00
abstract::We recently reported that tumor-directed antibodies could either stimulate, or inhibit, tumor progression, dependent upon the dosage used. The narrow range over which this immune response curve (IRC) occurs is surprising. Here we discuss features of the IRC, the mechanisms identified so far, and the potential clinical...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.29312
更新日期:2014-06-25 00:00:00
abstract::Searching for biomarkers that associated with the acquired resistance of malignant cells to epidermal growth factor receptor (EGFR)-targeting monoclonal antibodies is crucial to improve the clinical benefits of these therapeutic agents. We have recently demonstrated that molecular alterations in both oncogenic and imm...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.26904
更新日期:2013-12-01 00:00:00
abstract::Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitat...
journal_title:Oncoimmunology
pub_type: 评审
doi:10.4161/onci.25238
更新日期:2013-08-01 00:00:00
abstract:INTRODUCTION:Vaccination with dendritic cells (DCs) has generally not fulfilled its promise in cancer immunotherapy due to ineffective translation of immune responses into clinical responses. A proposed reason for this is intrinsic immune regulatory mechanisms, such as regulatory T cells (Tregs). A metronomic regimen o...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2016.1207842
更新日期:2016-07-08 00:00:00
abstract::The consensus Immunoscore is a routine assay quantifying the adaptive immune response within the tumor microenvironment. It has a prognostic value that has been confirmed in a phase 3 clinical trial (NCCTG N0147) in stage III colon cancers. Moreover, results from another phase 3 randomized trial revealed the predictiv...
journal_title:Oncoimmunology
pub_type: 杂志文章,评审
doi:10.1080/2162402X.2020.1796003
更新日期:2020-07-20 00:00:00
abstract::Although the proteasome inhibitor bortezomib has significantly improved the survival of patients with multiple myeloma (MM), the disease remains fatal as most patients eventually develop progressive disease. Recent data indicate that MM cells can evade bortezomib-induced cell death by undergoing autophagy as a consequ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1534664
更新日期:2018-11-02 00:00:00
abstract::Basophils play an important role in orienting Th2 immune response, and in the pathogenesis of allergic and inflammatory disorders. However, the mechanism by which basophils are kept in check remains unclear and hence we explored the role of regulatory T cells (Treg cells) in this process. We demonstrate that human Tre...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2020.1773193
更新日期:2020-06-05 00:00:00
abstract::Checkpoint inhibition has established immunotherapy as a major modality of cancer treatment. However, the success of cancer immunotherapy is still limited as immune regulation of tumor immunity is very complicated and mechanisms involved may also differ among cancer types. Beside checkpoints, other good candidates for...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1308616
更新日期:2017-03-31 00:00:00
abstract::Gamma delta T cells (γδT) are potent mediators of antitumor cytotoxicity and have shown promising efficacy in early phase clinical trials. Most is known about the tumoricidal properties of cells bearing the Vδ2 T cell receptor chain, but recent studies have demonstrated that cells with the Vδ1 chain and those with nei...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/2162402X.2014.973808
更新日期:2014-12-23 00:00:00
abstract::The DNA damage response (DDR), which is frequently activated in cancer cells, has been proposed to operate as an early barrier against oncogenesis. We have recently shown that ATM mediates the spontaneous regression of Eμ-myc-driven murine B-cell leukemia in a natural killer and T cell-dependent manner. The DDR partia...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.24438
更新日期:2013-06-01 00:00:00
abstract::The B7 family and tumor necrosis factor receptor (TNFR) superfamily play a vital role in the T-cell co-stimulatory and co-inhibitory pathways, regulating T-cell activation, tolerance, and exhaustion; therapeutic modulation of these pathways is translated into effective new cancer treatments. Better understanding of th...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1288329
更新日期:2017-02-16 00:00:00
abstract::Successful cancer immunotherapy is thought to require de novo priming of tumor specific CD8(+) T cells in lymphatic organs. Contrasting these beliefs, cancer therapy based on interleukin-10 (IL-10) results in tumor rejection without a requirement for T-cell trafficking from lymphatic organs. Rather, IL-10 directly act...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.21683
更新日期:2012-12-01 00:00:00
abstract::Immunogenic cell death (ICD) induced by anticancer chemotherapeutics is usually preceded by premortem stress affecting the endoplasmic reticulum (ER). This ER stress does not reflect a canonical unfolded protein response (UPR) but rather manifests solely at the level of the phosphorylation of eIF2α. eIF2α phosphorylat...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1431089
更新日期:2018-02-14 00:00:00
abstract::Immunotherapy with oncolytic herpes simplex virus-1 therapy offers an innovative, targeted, less-toxic approach for treating brain tumors. However, a major obstacle in maximizing oncolytic virotherapy is a lack of comprehensive understanding of the underlying mechanisms that unfold in CNS tumors/associated microenviro...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2019.1678921
更新日期:2019-10-21 00:00:00
abstract::Prognosis of glioblastoma remains dismal, underscoring the need for novel therapies. Immunotherapy is generating promising results, but requires combination strategies to unlock its full potential. We investigated the immunomodulatory capacities of poly(I:C) on primary human glioblastoma cells and its combinatorial po...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1407899
更新日期:2017-12-12 00:00:00
abstract::Oncology treatment has been revolutionized by the introduction of immune checkpoint inhibitor drugs, which enable 20-40% of patients to generate anti-tumor immune responses. Combination treatment approaches with chemotherapeutic drugs may enable responses in the remaining patient cohorts. In this regard, a handful of ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2019.1565859
更新日期:2019-01-22 00:00:00
abstract::The alarmin IL-33 is an IL-1 family member that stimulates pleiotropic immune reactions depending on the target tissue and microenvironmental factors. In this study, we have investigated the role of IL-33/ST2 axis in antitumor response to melanoma. Injection of IL-33 in mice-bearing subcutaneous B16.F10 melanoma resul...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1317420
更新日期:2017-04-20 00:00:00
abstract::In many cancers, regulatory T cells (Treg) play a crucial role in suppressing the effector immune response thereby permitting tumor development. Indeed, in mouse models, their depletion can promote the regression of tumors of various origins, including renal cell carcinoma when located subcutaneous (SC). In the presen...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/21624011.2014.963395
更新日期:2014-12-21 00:00:00
abstract::B cells are generally believed to operate as producers of high affinity antibodies to defend the body against microorganisms, whereas cellular cytotoxicity is considered as an exclusive prerogative of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In conflict with this dogma, recent studies have demonst...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.22354
更新日期:2012-11-01 00:00:00
abstract::Due to their constant exposure to inhaled antigens, lungs represent a particularly immunosuppressive environment that limits excessive immune responses; however, cancer cells can exploit this unique environment for their growth. We previously described the ability of aerosolized CpG-ODN combined with Poly(I:C) (TLR9 a...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2016.1234571
更新日期:2016-09-20 00:00:00
abstract::Preclinical data suggest that a "prime-boost" vaccine regimen using a target-expressing lentiviral vector for priming, followed by a recombinant protein boost, may be effective against cancer; however, this strategy has not been evaluated in a clinical setting. CMB305 is a prime-boost vaccine designed to induce a broa...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2020.1847846
更新日期:2020-11-19 00:00:00