Journal for Immunotherapy of Cancer This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Natural killer T cell activation increases iNOS + CD206 - M1 macrophage and controls the growth of solid tumor
ConclusionsWe showed that activation of NKT cell with α-GalCer modulates the frequency of M1-macrophages and effector Th1 cells in the secondary lymphoid tissues and tumor microenvironment and inhibit tumor growth. The finding suggests that activation of NKT cells with α-GalCer may provide an effective anti-cancer outcome. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 5, 2019 Category: Cancer & Oncology Source Type: research

MICA immune complex formed with alpha 3 domain-specific antibody activates human NK cells in a Fc-dependent manner
ConclusionsOur results demonstrate that an α3 domain-specific MICA antibody can circumvent sMICA-mediated suppression of NK cell cytolytic activity. Moreover, our data suggest that MICA immune complexes formed with α3-specific antibodies can activate NKG2D receptor and restore NK cell function in a Fc-dependent manner. The clinical utility of α3 domain-specific MICA/B antibodies may hold great promise as a new strategy for cancer immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 5, 2019 Category: Cancer & Oncology Source Type: research

Designing gene panels for tumor mutational burden estimation: the need to shift from ‘correlation’ to ‘accuracy’
AbstractTumor mutational burden (TMB) assessment is at the forefront in precision medicine. The TMB could represent a biomarker for immune checkpoint inhibitors (ICIs) responses. Whole exome sequencing (WES) is the gold standard to derive the TMB; while targeted next-generation sequencing panels might be more feasible. However, mainstream panels use ‘correlation’ (R2) between panel- and WES-based TMB to validate TMB estimation, which could be vulnerable to be distorted by cases with relatively ultra-high TMB within each cancer type. The FDA-approved FoundationOne CDx (F1CDx) panel-based TMB estimation seemed reliable (...
Source: Journal for Immunotherapy of Cancer - August 5, 2019 Category: Cancer & Oncology Source Type: research

Immunotherapy in small-cell lung cancer: from molecular promises to clinical challenges
AbstractManagement of small cell lung cancer (SCLC) has not changed over the last decades. In more recent years, alterations of DNA repair machinery and other molecular pathways have been identified in SCLC and preclinical data suggest that dysregulation of these pathways might offer new therapeutic opportunities.While immune checkpoint inhibitors (ICIs) have had a major impact on the clinical outcome of several solid tumors, including non-small cell lung cancer, the potential role of ICIs is currently under investigation in SCLC and some promising data are available. However, several clinical and biological hurdles have t...
Source: Journal for Immunotherapy of Cancer - August 4, 2019 Category: Cancer & Oncology Source Type: research

Local and abscopal responses in advanced intrahepatic cholangiocarcinoma with low TMB, MSS, pMMR and negative PD-L1 expression following combined therapy of SBRT with PD-1 blockade
ConclusionsThis study provided the first set of evidence for the effectiveness of SBRT and PD-1 blockade combined therapy in late-stage or recurrent ICC patients with low TMB, MSS, pMMR and negative PD-L1 expression, and potentially expanded the indications of the combined therapy to those patients who were previously not suitable for immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 4, 2019 Category: Cancer & Oncology Source Type: research

A case of checkpoint inhibitor-induced celiac disease
ConclusionsThere has been only one published case reporting ICI-induced celiac disease. Our case report highlights a rare irAE (celiac disease) associated with ICI treatment. It is unclear whether the patient had previously undiagnosed celiac disease or whether ICIs triggered her enteritis. Our patient was able to continue treatment with ICIs with dietary modifications, suggesting correct diagnosis is critical for optimal patient outcome. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 4, 2019 Category: Cancer & Oncology Source Type: research

State-of-the-art for CAR T-cell therapy for chronic lymphocytic leukemia in 2019
AbstractExperience in the use of CAR T cells to treat CLL is limited, but safety and efficacy data are encouraging, suggesting that it may be possible to use CAR T cells in populations of CLL patients with particularly unfavorable prognoses. Mechanisms intrinsic to the pathophysiology of CLL undoubtedly explain the efficacy reported based on limited data for the first few series, and underlie the rationale of successive modulations in lymphodepletion schemes, transgene constructs, and, finally, the therapeutic association of CAR T cells with ibrutinib, which appears to be particularly promising. This review describes the p...
Source: Journal for Immunotherapy of Cancer - July 31, 2019 Category: Cancer & Oncology Source Type: research

Targeting Interleukin(IL)-30/IL-27p28 signaling in cancer stem-like cells and host environment synergistically inhibits prostate cancer growth and improves survival
ConclusionThe lack of host leukocyte-derived IL-30 inhibits Tregs expansion, promotes intra-tumoral infiltration of CD4+T lymphocytes and cancer cell apoptosis. Concomitant lack of MDC influx, obtained by IL-30 silencing in PC-SLCs, boosts cytotoxic T lymphocyte activation and cancer cell apoptosis resulting in a synergistic tumor suppression with the prospective benefit of better survival for patients with advanced disease. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 30, 2019 Category: Cancer & Oncology Source Type: research

Combination therapy targeting both innate and adaptive immunity improves survival in a pre-clinical model of ovarian cancer
ConclusionsThis work highlights the importance of CD4+ T cells in tumor immunology. Furthermore, the data support the initiation of clinical trials in ovarian cancer that target both innate and adaptive immunity, with a focus on optimizing dosing schedules. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 29, 2019 Category: Cancer & Oncology Source Type: research

Perilesional edema in brain metastases: potential causes and implications for treatment with immune therapy
ConclusionsEdema itself should not preclude using anti-PD-1 with caution, as sensitive tumors have resultant decreases in edema, and anti-PD-1 itself does not exacerbate edema in sensitive tumors. Additional factors aside from tumor mass effect and vessel density cause perilesional edema. Melanoma cells themselves can cause decline in tight junction resistance in a system void of immune cells, suggesting they secrete factors that cause leakiness, which might be harnessed for pharmacologic targeting in patients with significant perilesional edema. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 29, 2019 Category: Cancer & Oncology Source Type: research

Epigenetic alterations are associated with tumor mutation burden in non-small cell lung cancer
ConclusionTo our knowledge, this is the first report for direct link between the methylome alterations and TMB in NSCLCs. High TMB NSCLCs had more DNAm aberrance and copy number variations (CNVs). In addition, the TMB distribution of Chinese NSCLCs population is lower than that of TCGA. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 25, 2019 Category: Cancer & Oncology Source Type: research

A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1 –3 inhibitor, cediranib, in recurrent women’s cancers with biomarker analyses
ConclusionsThe RP2D is tolerable and has preliminary activity in recurrent women ’s cancers. A phase 2 expansion study is now enrolling for recurrent ovarian cancer patients.Trial registrationClinicalTrials.gov identifier:NCT02484404. Registered June 29, 2015. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 24, 2019 Category: Cancer & Oncology Source Type: research

First-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody, in patients with advanced solid tumors
ConclusionsIT1208 monotherapy successfully depleted CD4+ T cells with a manageable safety profile and encouraging preliminary efficacy signals, which warrants further investigations, especially in combination with immune checkpoint inhibitors. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 23, 2019 Category: Cancer & Oncology Source Type: research

Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma
ConclusionsLocal therapy for oligoprogression after CPI can result in durable PFS in selected patients. We observed that patterns of failure seen during or after CPI treatment are strongly associated with PFS after local therapy, and may represent a useful criterion for patient selection. This experience suggests there may be an increased role for local therapy in patients being treated with immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 23, 2019 Category: Cancer & Oncology Source Type: research

Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma
ConclusionsGut microbiome may have a critical impact on the responses of HCC patients treated with anti-PD-1 immunotherapy. The dynamic variation characteristics of the gut microbiome may provide early predictions of the outcomes of immunotherapy in HCC, which is critical for disease-monitoring and treatment decision-making. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 22, 2019 Category: Cancer & Oncology Source Type: research