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 patients with melanoma. We showed that checkpoint molecules induced by ex vivo maturation correlated with in vivo DC vaccine activity. Melanoma patient DCs had reduced expression of cell surface inducible T-cell costimulator ligand (ICOSL) and had defective intrinsic NF-κB signaling. Chromatin immunoprecipitation assays revealed NF-κB-dependent transcriptional regulation of ICOSL expression by DCs. Blockade of ICOSL on DCs reduced priming of antigen-specific CD8+ and CD4+ T cells from naïve donors in vitro Concentration of extracellular/soluble ICOSL released from vaccine DCs positively correlated with patient clinical outcomes, which we showed to be partially regulated by ADAM10/17 sheddase activity. These data point to the critical role of canonical NF-κB signaling, the regulation of matrix metalloproteinases, and DC-derived ICOSL in the specific priming of cognate T-cell responses in the cancer setting. This study supports the implementation of targeted strategies to augment these pathways for improved immunotherapeutic outcomes in patients with cancer.
journal_name
Cancer Immunol Resjournal_title
Cancer immunology researchauthors
Maurer DM,Adamik J,Santos PM,Shi J,Shurin MR,Kirkwood JM,Storkus WJ,Butterfield LHdoi
10.1158/2326-6066.CIR-20-0274subject
Has Abstractpub_date
2020-12-01 00:00:00pages
1554-1567issue
12eissn
2326-6066issn
2326-6074pii
2326-6066.CIR-20-0274journal_volume
8pub_type
杂志文章abstract::Colorectal cancer consists of a small number of cancer stem cells (CSC) and many non-CSCs. Although rare in number, CSCs are a target for cancer therapy, because they survive conventional chemo- and radiotherapies and perpetuate tumor formation in vivo In this study, we conducted an HLA ligandome analysis to survey HL...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0518
更新日期:2018-03-01 00:00:00
abstract::The presence and activity of CD8+ T cells within the tumor microenvironment are essential for the control of tumor growth. Utilizing B16-F10 melanoma tumors that express altered peptide ligands of chicken ovalbumin, OVA257-264, we measured high- and low-affinity OVA-specific responses following adoptive transfer of OT...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0690
更新日期:2020-04-01 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::CD169 (sialoadhesin) is a sialic acid receptor that is specifically expressed on macrophages, including lymph node sinus macrophages. Animal studies suggest that CD169(+) macrophages in lymph nodes have properties in preventing cancers. In order to determine the significance of CD169(+) macrophages in patients with ma...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-14-0180
更新日期:2015-12-01 00:00:00
abstract::CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously experienced CD137 ligation. Epigenetic changes could provide a suitable mechanism for these long-term consequences. Genome-wide DNA methylation arrays were carried out on human peripheral blood CD...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0159
更新日期:2018-01-01 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::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::Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that phenotypically resemble conventional secondary lymphoid organs and are commonly found at sites of chronic inflammation. They are also found in a wide variety of primary and metastatic human tumors. The presence of tumor-associated TLS (TA-TLS) is ...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-20-0432
更新日期:2020-11-01 00:00:00
abstract::Natural killer cell (NKc)-based therapies offer promising outcomes in patients with tumors, but they could improve with appropriate selection of donors and optimization of methods to expand NKcs in vitro Education through licensing interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) and NKG2A w...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0022
更新日期:2018-12-01 00:00:00
abstract::Many immunotherapeutic approaches under development rely on T-cell recognition of cancer-derived peptides bound to human leukocyte antigen molecules on the cell surface. Direct experimental demonstration that such peptides are processed and bound is currently challenging. Here, we describe a method that meets this cha...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0107
更新日期:2019-11-01 00:00:00
abstract::Tumor-infiltrating lymphocytes (TIL) in colorectal cancer liver metastases (CLM) have been associated with more favorable patient outcomes, but whether MHC class I (MHC-I) expression on cancer cells affects prognosis is uncertain. Immunohistochemistry was performed on a tissue microarray of 158 patients with CLM, who ...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-13-0180
更新日期:2014-06-01 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::Advanced and metastatic squamous cell carcinomas (SCC) are common and difficult-to-treat malignancies. We assessed 75 immunotherapy-treated patients with SCC from a clinically annotated database of 2,651 patients, as well as 9,407 patients from a deidentified database for molecular features that might influence checkp...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0716
更新日期:2019-06-01 00:00:00
abstract::Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. ...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0400
更新日期:2017-08-01 00:00:00
abstract::Ipilimumab and radiotherapy are commonly used to treat unresectable and metastatic melanoma. Results from preclinical studies and case reports suggest a biologic interaction between these two treatments. To understand the clinical implications of the interaction, we carried out a retrospective study reviewing records ...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-13-0082
更新日期:2013-08-01 00:00:00
abstract::MHC-bound peptides from aberrant proteins may be a specific immunotherapeutic target on cancer cells. Because of difficulties in identifying such antigens, viral or model antigens have so far been used to study their biological relevance. We here identify a naturally existing human T-cell epitope derived from a trunca...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0137
更新日期:2019-05-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy characterized by a paucity of tumor-proximal CD8+ T cells and resistance to immunotherapeutic interventions. Cancer-associated mechanisms that elicit CD8+ T-cell exclusion and resistance to immunotherapy are not well-known. Here, using a Kras- and p53-...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0349
更新日期:2020-03-01 00:00:00
abstract::Individuals of African descent are disproportionately affected by specific complex diseases, such as breast and prostate cancer, which are driven by both biological and nonbiological factors. In the case of breast cancer, there is clear evidence that psychosocial factors (environment, socioeconomic status, health beha...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-18-0564
更新日期:2019-09-01 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::The relationship between the adaptive CD4+ T cell response and human cancer is unclear. The oncofetal antigen 5T4 is expressed on many human carcinomas, including colorectal cancer (CRC) cells, but has limited expression on normal tissues. We previously identified anti-5T4 CD4+ T cells in a proportion of CRC patients,...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-13-0035
更新日期:2013-12-01 00:00:00
abstract::Accumulating preclinical and clinical evidence indicates that the success of several anticancer agents-including some conventional chemotherapeutics, targeted anticancer agents as well as specific forms of radiotherapy-depends (at least in part) on their ability to stimulate anticancer immune responses. Such immunosti...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-16-0197
更新日期:2016-11-01 00:00:00
abstract::Multiple myeloma is characterized by the clonal expansion of malignant plasma cells in the bone marrow. But the phenotypic diversity and the contribution of less predominant B-lineage clones to the biology of this disease have been controversial. Here, we asked whether cells bearing the dominant multiple myeloma immun...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0012
更新日期:2017-09-01 00:00:00
abstract::Ipilimumab, a novel immune checkpoint inhibitor, is associated with long-term survival in approximately 20% of patients with advanced melanoma and is also being evaluated in the adjuvant setting. With this growing cohort of survivors, long-term health outcomes, chronic toxicities, and functional outcomes among survivo...
journal_title:Cancer immunology research
pub_type: 临床试验,杂志文章
doi:10.1158/2326-6066.CIR-14-0217
更新日期:2015-05-01 00:00:00
abstract::The prognosis is very dismal for patients with relapsed CD20(+) B-cell non-Hodgkin lymphoma (B-NHL). Facilitating the development of alternative novel therapeutic strategies is required to improve outcomes in patients with recurrent/refractory CD20(+) B-NHL. In this study, we investigated functional activities of anti...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-14-0114
更新日期:2015-04-01 00:00:00
abstract::Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-pa...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0125
更新日期:2017-03-01 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::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::Ligation of GITR (glucocorticoid-induced tumor necrosis factor (TNF) receptor-related gene, or TNFRSF18) by agonist antibody has recently entered into early phase clinical trials for the treatment of advanced malignancies. Although the ability of GITR modulation to induce tumor regression is well-documented in preclin...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-13-0086
更新日期:2013-11-01 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::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