Abstract:
:We conducted in vitro studies and a clinical trial for patients with squamous cell carcinoma of the head and neck (SCCHN) to study the relationship between FcγRIIIa polymorphisms and antibody-dependent cellular cytotoxicity (ADCC). In vitro, FcγRIIIa genotype was correlated with ADCC and innate cytotoxicity using natural killer (NK) cells harvested from healthy donors. In the phase II study, patients with recurrent or metastatic SCCHN were treated with cetuximab (500 mg/m(2) i.v. every 2 weeks) and lenalidomide (25 mg daily). FcγRIIIa genotype and ex vivo ADCC were correlated with clinical response, progression-free survival (PFS), and overall survival (OS). In vitro, healthy donors with a FcγRIIIa 158-V allele demonstrated more effective ADCC against two colon cancer cell lines HT29 and SW480, mean cytotoxicity: FF 16.1%, VF/VV 24.3% (P = 0.015) and FF 11.7%, VF/VV 21.0% (P = 0.008), respectively. We observed a linear relationship between ADCC response and innate cytotoxicity. In the phase II trial, 40 patients received cetuximab and lenalidomide with median PFS of 7.2 weeks and OS of 16.4 weeks. Thirty-six patients had FcγRIIIa genotype: VV (2), VF (20), and FF (14), and 25 patients had sufficient NK-cell yield to perform ex vivo ADCC. FcγRIIIa genotype was not associated with any clinical outcomes. Patients mounting ex vivo ADCC response had a higher likelihood of stable disease (P = 0.01) and showed a trend toward increased PFS: 14 weeks versus 6.8 weeks, respectively (P = 0.13). Enhanced ex vivo ADCC and innate immunity responses were more predictive of clinical response than FcγRIIIa and may offer a functional assay to select patients suitable for cetuximab therapy.
journal_name
Cancer Immunol Resjournal_title
Cancer immunology researchauthors
Taylor RJ,Saloura V,Jain A,Goloubeva O,Wong S,Kronsberg S,Nagilla M,Silpino L,de Souza J,Seiwert T,Vokes E,Villaflor V,Cohen EEdoi
10.1158/2326-6066.CIR-14-0188subject
Has Abstractpub_date
2015-05-01 00:00:00pages
567-74issue
5eissn
2326-6066issn
2326-6074pii
2326-6066.CIR-14-0188journal_volume
3pub_type
杂志文章,多中心研究abstract::Natural killer (NK) cells contribute to clinical responses in patients treated with rituximab, but the rules determining NK-cell responsiveness to mAb therapies are poorly defined. A deeper understanding of the mechanisms responsible for antibody-dependent cellular cytotoxicity (ADCC) could yield useful biomarkers for...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-13-0158
更新日期:2014-09-01 00:00:00
abstract::The antibodies produced initially in response to most antigens are high molecular weight (MW) immunoglobulins (IgM) with low affinity for the antigen, while the antibodies produced later are lower MW classes (e.g., IgG and IgA) with, on average, orders of magnitude higher affinity for that antigen. These changes, ofte...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-14-0029
更新日期:2014-05-01 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::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::Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Less than 6% of patients survive beyond the fifth year due to inadequate early diagnostics and ineffective treatment options. Our laboratory has developed an allogeneic, granulocyte-macrophage colony-stimulating factor (GM-CSF...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0200-T
更新日期:2016-03-01 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::One of the obstacles for cancer immunotherapy is the inefficiency of CD8(+) T-cell recruitment to tumors. STAT3 has been shown to suppress CD8(+) T-cell antitumor functions in various cancer models, in part by restricting accumulation of CD8(+) T cells. However, the underlying molecular mechanism by which STAT3 in CD8...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0014
更新日期:2015-08-01 00:00:00
abstract::The cytokine IL15 is required for survival and activation of natural killer (NK) cells as well as expansion of NK-cell populations. Here, we compare the effects of continuous IL15 infusions on NK-cell subpopulations in cancer patients. Infusions affected the CD56bright NK-cell subpopulation in that the expansion rates...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0279
更新日期:2017-10-01 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::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
更新日期:2018-06-01 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::Macrophage-mediated cytotoxicity is controlled by surface receptor expression and activation. Despite the numerous studies documenting the role of macrophage C-type lectin receptors (CLR) in pathogen elimination, little is known about their contribution to antitumor responses. Here, we report that IL13 inhibits T-cell...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0213
更新日期:2019-02-01 00:00:00
abstract::The importance of natural killer (NK) cells in the early immune response to viral or bacterial infection is well known. However, the phenotype, function, and physiologic role of NK cells during the late stage of persistent viral infection have not been extensively studied. Here, we characterized NK cells in mice persi...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0403
更新日期:2019-04-01 00:00:00
abstract::Recruitment of myeloid-derived suppressor cells (MDSC) into the tumor microenvironment (TME) contributes to cancer immune evasion. MDSCs express the chemokine receptor CXCR2, and inhibiting CXCR2 suppresses the recruitment of MDSCs into the tumor and the premetastatic niche. Here, we compared the growth and metastasis...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-20-0312
更新日期:2020-11-11 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::Immune checkpoint inhibitors are promising treatments for patients with a variety of malignancies. Toward understanding the determinants of response to immune checkpoint inhibitors, it was previously demonstrated that the presence of somatic mutations is associated with benefit from checkpoint inhibition. A hypothesis...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0019
更新日期:2017-01-01 00:00:00
abstract::Regulatory T cells (Treg) have long been considered one-sided suppressors of antitumor immune responses and hence associated with poor patient outcome in cancer. However, evidence is mounting of a paradoxical positive prognostic effect of Tregs on certain malignancies, including urinary bladder cancer (UBC). This disc...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0466
更新日期:2018-05-01 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::Granulocytic-macrophage colony-stimulating factor (GM-CSF) is used as an adjuvant in cancer vaccine trials and has the potential to enhance antitumor efficacy with immunotherapy; however, its immunologic effects are not fully understood. Here, we report results from a phase I study of neoadjuvant GM-CSF in patients wi...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0042
更新日期:2016-11-01 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::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::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::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::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::Immunotherapy with monoclonal antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1) has improved the survival of patients with metastatic melanoma. These agents carry a certain risk of adverse immune-related events. We present a patient with widely metastatic melanoma who was...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0141
更新日期:2015-12-01 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::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::Ligand-receptor complexes play a central role in mediating a range of processes in immunology and cancer biology. The ability to directly quantify the fraction of receptors occupied by a ligand in a given biospecimen, as opposed to assessing the concentration of ligand and receptor separately, could provide an additio...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0821
更新日期:2019-09-01 00:00:00
abstract::Solid tumors are refractory to cellular immunotherapies in part because they contain suppressive immune effectors such as myeloid-derived suppressor cells (MDSCs) that inhibit cytotoxic lymphocytes. Strategies to reverse the suppressive tumor microenvironment (TME) should also attract and activate immune effectors wit...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0572
更新日期:2019-03-01 00:00:00
abstract::Pneumonitis may complicate anti-programmed death-1 (PD-1) therapy, although symptoms usually resolve with steroids. The long-term effects on respiratory function, however, are not well defined. We screened melanoma patients treated with anti-PD-1, with and without ipilimumab (anti-CTLA-4), and identified 31 patients w...
journal_title:Cancer immunology research
pub_type: 杂志文章,多中心研究
doi:10.1158/2326-6066.CIR-18-0717
更新日期:2019-11-01 00:00:00