Abstract:
:Caspase recuitment domain-containing protein 9 (CARD9) functions in different inflammation pathways to elicit responses to microbial signals and is known to affect intestinal inflammation. Examining the APC(min) mouse model of intestinal tumorigenesis and using stringently controlled, sex- and age-matched pairs of CARD9-competent and CARD9-deficient mice, we have found that CARD9 has a restricted but strong effect on tumorigenesis in the large intestine. We have found that CARD9 reduces viability specifically in males and promotes tumorigenesis specifically in the large intestines of these male mice. To our knowledge, this is the first gene ablation in APC(min) mice that solely affects colon tumors in male subjects and, as such, may have significant clinical implications. Additional data suggest correlative disruption of plasma cytokine expression and immune infiltration of the tumors. We speculate that known sex-specific differences in human colorectal cancer may involve inflammation, particularly CARD9-dependent inflammation.
journal_name
Cancer Immunol Resjournal_title
Cancer immunology researchauthors
Leo VI,Tan SH,Bergmann H,Cheah PY,Chew MH,Lim KH,Ruland J,Reilly PTdoi
10.1158/2326-6066.CIR-14-0148subject
Has Abstractpub_date
2015-07-01 00:00:00pages
721-6issue
7eissn
2326-6066issn
2326-6074pii
2326-6066.CIR-14-0148journal_volume
3pub_type
杂志文章abstract::Hypoxia-driven, A2A adenosine receptor (A2AR)-mediated (hypoxia-A2-adenosinergic), T-cell-autonomous immunosuppression was first recognized as critical and nonredundant in protecting normal tissues from inflammatory damage and autoimmunity. However, this immunosuppressive mechanism can be highjacked by bacteria and tu...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-14-0075
更新日期:2014-07-01 00:00:00
abstract::Type I interferon (IFN-I) is a class of antiviral immunomodulatory cytokines involved in many stages of tumor initiation and progression. IFN-I acts directly on tumor cells to inhibit cell growth and indirectly by activating immune cells to mount antitumor responses. To understand the role of endogenous IFN-I in spont...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0675
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abstract::Preventive vaccination against tumor-associated endogenous antigens is considered to be an attractive strategy for the induction of a curative immune response concomitant with a long-lasting immunologic memory. The mucin MUC1 is a promising tumor antigen, as its tumor-associated form differs from the glycoprotein form...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0256
更新日期:2019-01-01 00:00:00
abstract::Macroenvironmental factors, including a patient's physical and social environment, play a role in cancer risk and progression. Our previous studies show that living in an enriched environment (EE) providing complex stimuli confers an anticancer phenotype in mice mediated, in part by a specific neuroendocrine axis, wit...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0297
更新日期:2016-06-01 00:00:00
abstract::Modulating the function of immune receptors with antibodies is ushering in a new era in cancer immunotherapy. With the notable exception of PD-1 blockade used as monotherapy, immune modulation can be associated with significant toxicities that are expected to escalate with the development of increasingly potent immune...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-15-0194
更新日期:2015-11-01 00:00:00
abstract::Radiotherapy (RT) represents one of the main anticancer approaches for the treatment of solid tumors. Beyond the expected direct effects of RT on tumor cells, evidence supporting the importance of an immune response to RT is growing. The balance between RT-mediated immunogenic and tolerogenic activity is ill-defined a...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0633
更新日期:2019-03-01 00:00:00
abstract::Despite HER2-targeted therapies improving the outcome of HER2+ breast cancer, many patients experience resistance and metastatic progression. Cancer stem cells (CSC) play a role in this resistance and progression, thus combining HER2 targeting with CSC inhibition could improve the management of HER2+ breast cancer. Th...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-20-0082
更新日期:2020-08-01 00:00:00
abstract::On September 25-28, 2016, in New York City, the Second International Cancer Immunotherapy Conference was cohosted by the Cancer Research Institute, the American Association for Cancer Research, the Association for Cancer Immunotherapy, and the European Academy of Tumor Immunology. This exciting conference brought toge...
journal_title:Cancer immunology research
pub_type:
doi:10.1158/2326-6066.CIR-16-0276
更新日期:2016-12-01 00:00:00
abstract::Although immune checkpoint blockade (ICB) improves clinical outcome in several types of malignancies, pancreatic ductal adenocarcinoma (PDA) remains refractory to this therapy. Preclinical studies have demonstrated that the relative abundance of suppressive myeloid cells versus cytotoxic T cells determines the efficac...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0661
更新日期:2020-03-01 00:00:00
abstract::Chimeric antigen receptor (CAR) T-cell therapy is effective in the treatment of cancers of hematopoietic origin. In the immunosuppressive solid tumor environment, CAR T cells encounter obstacles that compromise their efficacy. We developed a strategy to address these barriers by having CAR T cells secrete single-domai...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0734
更新日期:2020-04-01 00:00:00
abstract::Natural killer T (NKT) cells are glycolipid-reactive lymphocytes that promote cancer control. In previous studies, NKT-cell activation improved survival and antitumor immunity in a postsurgical mouse model of metastatic breast cancer. Herein, we investigated whether NKT-cell activation could be combined with chemother...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0229
更新日期:2017-12-01 00:00:00
abstract::Antibody-drug conjugates (ADC) are emerging as powerful treatment strategies with outstanding target-specificity and high therapeutic activity in patients with cancer. Brentuximab vedotin represents a first-in-class ADC directed against CD30(+) malignancies. We hypothesized that its sustained clinical responses could ...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-13-0198
更新日期:2014-08-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is a B-cell neoplasia characterized by protumor immune dysregulation involving nonmalignant cells of the microenvironment, including T lymphocytes and tumor-associated myeloid cells. Although therapeutic agents have improved treatment options for CLL, many patients still fail to resp...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0152
更新日期:2019-12-01 00:00:00
abstract::The TNF receptor family member OX40 promotes activation and proliferation of T cells, which fuels efforts to modulate this immune checkpoint to reinforce antitumor immunity. Besides T cells, NK cells are a second cytotoxic lymphocyte subset that contributes to antitumor immunity, particularly in leukemia. Accordingly,...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0212
更新日期:2018-02-01 00:00:00
abstract::We assessed the contribution of IL1 signaling molecules to malignant tumor growth using IL1β-/-, IL1α-/-, and IL1R1-/- mice. Tumors grew progressively in IL1R-/- and IL1α-/- mice but were often absent in IL1β-/- mice. This was observed whether tumors were implanted intradermally or injected intravenously and was true ...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0552
更新日期:2020-05-01 00:00:00
abstract::The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related a...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0220
更新日期:2018-04-01 00:00:00
abstract::Efficacious antitumor immune responses must overcome multiple suppressive mechanisms in the tumor microenvironment to control cancer progression. In this study, we demonstrate that dual targeting of suppressive myeloid populations by inhibiting CSF-1/CSF-1R signaling and activation of antigen-presenting cells with ago...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0258
更新日期:2017-12-01 00:00:00
abstract::Activation of YAP, a Hippo pathway effector, is an important resistance mechanism to BRAF inhibitor (BRAFi) in melanoma. Emerging evidence also suggests that YAP is involved in suppression of the antitumor immune response. However, the potential direct impact of YAP activity on cytotoxic T-cell immune responses has no...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0320
更新日期:2018-03-01 00:00:00
abstract::In the past five decades, the role for lymphocytes in host immune response to tumors has been shown, at least in some patients, to be a critical component in disease prognosis. Also, the heterogeneity of lymphocytes has been documented, including the existence of regulatory T cells that suppress the immune response. A...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-15-0143
更新日期:2015-08-01 00:00:00
abstract::Freeze-dried black raspberries (BRB), their component anthocyanins (AC), and a metabolite of BRB ACs, protocatechuic acid (PCA), inhibit the development of esophageal cancer in rats induced by the carcinogen, N-nitrosomethylbenzylamine (NMBA). All three components reduce inflammation in the esophagus and in plasma. Th...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0091
更新日期:2016-01-01 00:00:00
abstract::New immunotherapeutic strategies are needed to induce effective antitumor immunity in all cancer patients. Malignant mesothelioma is characterized by a poor prognosis and resistance to conventional therapies. Infiltration of tumor-associated macrophages (TAM) is prominent in mesothelioma and is linked to immune suppre...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0309
更新日期:2017-07-01 00:00:00
abstract::Vaccinia virus (VACV) is a double-stranded DNA virus that devotes a large portion of its 200 kbp genome to suppressing and manipulating the immune response of its host. Here, we investigated how targeted removal of immunomodulatory genes from the VACV genome impacted immune cells in the tumor microenvironment with the...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0703
更新日期:2020-05-01 00:00:00
abstract::Therapeutic cancer vaccines targeting melanoma-associated antigens are commonly immunogenic but are rarely effective in promoting objective clinical responses. To identify critical molecules for activation of effective antitumor immunity, we have profiled autologous dendritic cell (DC) vaccines used to treat 35 patien...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-20-0274
更新日期:2020-12-01 00:00:00
abstract::With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated and maintained on the FVB geneti...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0298
更新日期:2018-06-01 00:00:00
abstract::Blockade of the pathway including programmed death-ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) has produced clinical benefits in patients with a variety of cancers. Elevated levels of soluble PD-L1 (sPD-L1) have been associated with worse prognosis in renal cell carcinoma and multiple myel...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0329
更新日期:2017-06-01 00:00:00
abstract::Triple-negative breast cancer (TNBC) cells are modulated in reaction to tumor-infiltrating lymphocytes. However, their specific responses to this immune pressure are unknown. In order to address this question, we first used mRNA sequencing to compare the immunophenotype of the TNBC cell line MDA-MB-231 and the luminal...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0182
更新日期:2017-04-01 00:00:00
abstract::Delayed radiation-induced vasculitic leukoencephalopathy related to stereotactic radiosurgery (SRS) of brain metastases has been reported to manifest clinically 9 to 18 months after treatment. Immune-modulating therapies have been introduced to treatment regimens for malignancies with metastatic predilection to the br...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0238
更新日期:2016-06-01 00:00:00
abstract::T-cell receptor (TCR) gene therapy is a promising next-generation antitumor treatment. We previously developed a single-T-cell analysis protocol that allows the rapid capture of paired TCRα and β cDNAs. Here, we applied the protocol to analyze the TCR repertoire of tumor-infiltrating lymphocytes (TIL) of various cance...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0489
更新日期:2018-04-01 00:00:00
abstract::In the context of cancer, naïve T cells are insufficiently primed and become progressively dysfunctional. Boosting antitumor responses by blocking PD-1 or CTLA-4 results in durable clinical responses only in a limited proportion of cancer patients, suggesting that other pathways must be targeted to improve clinical ef...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0103-T
更新日期:2015-11-01 00:00:00
abstract::Monoclonal antibodies (mAb) can modulate cancer cell signal transduction and recruit antitumor immune effector mechanisms-including antibody-dependent cellular cytotoxicity (ADCC). Although several clinically effective antibodies can promote ADCC, therapeutic resistance is common. We hypothesized that oncogenic signal...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-14-0083
更新日期:2014-12-01 00:00:00