The clinical application of cancer immunotherapy based on naturally circulating dendritic cells
AbstractDendritic cells (DCs) can initiate and direct adaptive immune responses. This ability is exploitable in DC vaccination strategies, in which DCs are educated ex vivo to present tumor antigens and are administered into the patient with the aim to induce a tumor-specific immune response. DC vaccination remains a promising approach with the potential to further improve cancer immunotherapy with little or no evidence of treatment-limiting toxicity. However, evidence for objective clinical antitumor activity of DC vaccination is currently limited, hampering the clinical implementation. One possible explanation for this i...
Source: Journal for Immunotherapy of Cancer - April 18, 2019 Category: Cancer & Oncology Source Type: research

Treatment of malignant pleural effusions: the case for localized immunotherapy
AbstractMalignant pleural effusions (MPE) are a common terminal pathway for many cancers, with an estimated United States incidence of more than 150,000 cases per year. MPE is an aggressive disease with a uniformly fatal prognosis and a life expectancy of only 3 to 12  months. The development of an effective targeted therapy represents a pressing unmet need. This commentary focuses on how cellular and humoral components condition the pleural space as a tumor-promoting, wound-healing environment. Despite an abundance of potential antigen presenting and effector cells in the pleura, their physical isolation by the mes...
Source: Journal for Immunotherapy of Cancer - April 18, 2019 Category: Cancer & Oncology Source Type: research

Exploring the emerging role of the microbiome in cancer immunotherapy
AbstractThe activity of the commensal microbiota significantly impacts human health and has been linked to the development of many diseases, including cancer. Gnotobiotic animal models have shown that the microbiota has many effects on host physiology, including on the development and regulation of immune responses. More recently, evidence has indicated that the microbiota can more specifically influence the outcome of cancer immunotherapy. Therapeutic interventions to optimize microbiota composition to improve immunotherapy outcomes have shown promise in mouse studies. Ongoing endeavors are translating these pre-clinical ...
Source: Journal for Immunotherapy of Cancer - April 17, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis
Following publication of the original article [1], the authors reported an error in their listed affiliations. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 17, 2019 Category: Cancer & Oncology Source Type: research

Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature
ConclusionsSOT recipients had a high allograft rejection rate that was observed shortly after CPI initiation, with high mortality rates. Further studies are needed to optimize the anticancer treatment approach in these patients. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 16, 2019 Category: Cancer & Oncology Source Type: research

Immunogenicity of immunomodulatory, antibody-based, oncology therapeutics
AbstractThe increasing use of multiple immunomodulatory (IMD) agents for cancer therapies (e.g. antibodies targeting immune checkpoints, bispecific antibodies, and chimeric antigen receptor [CAR]-T cells), is raising questions on their potential immunogenicity and effects on treatment. In this review, we outline the mechanisms of action (MOA) of approved, antibody-based IMD agents, potentially related to their immunogenicity, and discuss the reported incidence of anti-drug antibodies (ADA) as well as their clinical relevance in patients with cancer. In addition, we discuss the impact of the administration route and potenti...
Source: Journal for Immunotherapy of Cancer - April 15, 2019 Category: Cancer & Oncology Source Type: research

CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids
ConclusionsBased on these preclinical findings, heterogeneity and plasticity of CEA expression appear to confer low cibisatamab sensitivity in PDOs, supporting further clinical evaluation of their predictive effect in CRC. Pharmacological inhibition of the WNT/ β-catenin pathway may be a rational combination to sensitize CRCs to cibisatamab. Our novel PDO and T cell co-culture immunotherapy models enable pre-clinical discovery of candidate biomarkers and combination therapies that may inform and accelerate the development of immuno-oncology agents in the clinic. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 15, 2019 Category: Cancer & Oncology Source Type: research

The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation
ConclusionsBy targeting CTLA-4 and OX40 simultaneously, ATOR-1015 is directed to the tumor area where it induces enhanced immune activation, and thus has the potential to be a next generation CTLA-4 targeting therapy with improved clinical efficacy and reduced toxicity. ATOR-1015 is also expected to act synergistically with anti-PD-1/PD-L1 therapy. The pre-clinical data support clinical development of ATOR-1015, and a first-in-human trial has started (NCT03782467). (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 11, 2019 Category: Cancer & Oncology Source Type: research

Stereotactic radiosurgery combined with nivolumab or Ipilimumab for patients with melanoma brain metastases: evaluation of brain control and toxicity
ConclusionsConcurrent SRS and ipilimumab or nivolumab show meaningful intracranial activity in patients with either asymptomatic and symptomatic melanoma brain metastases, although a subset of patients may develop symptomatic RN. The combination of nivolumab with SRS is associated with better intracranial control. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 11, 2019 Category: Cancer & Oncology Source Type: research

Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial
ConclusionsActivated T cells in the tumor microenvironment are associated with pCR whereas stromal functions are associated with residual disease. Most immune functions decrease during neoadjuvant chemotherapy but several immunotherapy targets (PD-L1, IL6, IL8) remain expressed in RD suggesting potential therapeutic strategies. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 10, 2019 Category: Cancer & Oncology Source Type: research

Effective cancer immunotherapy by natural mouse conventional type-1 dendritic cells bearing dead tumor antigen
ConclusionsThis preclinical proof-of-principle study is first to support the therapeutic efficacy of cancer immunotherapy with syngeneic dead tumor cell antigen-loaded mouse cDC1s, the equivalents of the human dendritic cell subset that correlates with beneficial prognosis of cancer patients. Our data pave the way for translation of cDC1-based cancer treatments into the clinic when isolation of natural human cDC1s becomes feasible. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 8, 2019 Category: Cancer & Oncology Source Type: research

Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program
ConclusionsThe appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 3, 2019 Category: Cancer & Oncology Source Type: research

Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040)
AbstractTwo phase III clinical trials (CheckMate 141 and KEYNOTE 040) have independently demonstrated that overall survival (OS) in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, who have failed platinum-based therapy, can be improved with anti-PD1 monotherapy. Treatment with nivolumab or pembrolizumab in R/M HNSCC patients led to an improved OS with a hazards ratio (HR) of 0.70 (95%CI 0.51 –0.96;p = 0.01) and HR of 0.80 (95%CI 0.65–0.98,p = 0.0161), respectively, as compared to standard of care (SOC) chemo monotherapy regimens (specifically, ...
Source: Journal for Immunotherapy of Cancer - April 3, 2019 Category: Cancer & Oncology Source Type: research

Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report
ConclusionThe severe systemic inflammatory reaction and impaired peripheral circulation in this patient was attributed to excessive immunological effect induced by nivolumab resulting in cytokine release syndrome (CRS). This is the first report of a patient with multiple pathological conditions including HLH, TTP-like condition, and PF presumably arising from ICI-induced CRS. Further accumulating thoroughly investigated cases would lead to better understanding of the disease and development of reliable cancer immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 3, 2019 Category: Cancer & Oncology Source Type: research

The correlations of tumor mutational burden among single-region tissue, multi-region tissues and blood in non-small cell lung cancer
AbstractHigh-level tissue tumor mutational burden (tTMB) or blood TMB (bTMB) are associated with better response of immunotherapy in non-small cell lung cancer (NSCLC) patients. However, the correlations of single-region tTMB, multi-region tTMB and bTMB remain to be determined. Moreover, whether intratumor heterogeneity (ITH) has impact on TMB should be clarified. We collected multi-region tumor tissues with matched blood from 32 operative NSCLC and evaluated single-region tTMB, multi-region tTMB and bTMB through a 1021-gene panel sequencing. TMB of>  9 mutations/Mb was classified as high. Besides, we used tTMB f...
Source: Journal for Immunotherapy of Cancer - April 3, 2019 Category: Cancer & Oncology Source Type: research

Early introduction of selective immunosuppressive therapy associated with favorable clinical outcomes in patients with immune checkpoint inhibitor –induced colitis
AbstractBackgroundCurrent treatment guidelines for immune-mediated colitis (IMC) recommend 4 to 6  weeks of steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) in patients who do not respond to steroids. We assessed the effect of early SIT introduction and number of SIT infusions on clinical outcomes.MethodsWe performed a retrospective review of patients with IMC who received SIT at The University of Texas MD Anderson Cancer Center between January and December 2018. Logistic regression analyses were used to assess associations between clinical outcomes an...
Source: Journal for Immunotherapy of Cancer - April 2, 2019 Category: Cancer & Oncology Source Type: research

Could the menagerie of the gut microbiome really cure cancer? Hope or hype
AbstractThe investigational scale of the gut microbiome is expanding rapidly. In 2018, the intersection of gut microbiota and immuno-oncology received much attention. While the impact of gut microbiota on the immune system was already established, the year received an exponential expansion of microbiome ’s role in the immunotherapy setting. The microbiome research pipeline is ripe for large-scale, prospective trials. Working knowledge of immune-based cancer treatments, heterogeneity in their responses and resistance mechanisms, relevant immunological and microbiological pathways and potential for gut microbiome in en...
Source: Journal for Immunotherapy of Cancer - April 2, 2019 Category: Cancer & Oncology Source Type: research

Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T  cell immunity
ConclusionOur data show the importance of specific expression of Notch ligands on DCs in the regulation of T-cell effector function. Thus, strategies incorporating selectively engineered Notch ligands could provide a novel approach of therapeutics for modulating immunity in various immunosuppressive conditions including cancer. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 2, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Therapeutic efficacy, pharmacokinetic profiles, and toxicological activities of humanized antibody-drug conjugate Zt/g4-MMAE targeting RON receptor tyrosine kinase for cancer therapy
Following publication of the original article [1], the author reported two errors in the authors affiliations: (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 2, 2019 Category: Cancer & Oncology Source Type: research

Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition
AbstractBackgroundA male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting.MethodsAdvanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or niv...
Source: Journal for Immunotherapy of Cancer - March 29, 2019 Category: Cancer & Oncology Source Type: research

Interaction of host immunity with HER2-targeted treatment and tumor heterogeneity in HER2-positive breast cancer
AbstractGrowing evidence suggests a clear role of the host immune system in HER2+ breast cancer. In addition, HER2+ breast cancer is generally considered more immunogenic than hormone receptor-positive (HR+)/HER2-, and specific molecular HER2+ subgroups (e.g. HER2-enriched disease) are more immunogenic than others (e.g. Luminal A or B). From a clinical perspective, the immune system plays a relevant prognostic role in HER2+ breast cancer and contributes to the therapeutic effects of trastuzumab. However, as more HER2-targeted agents become available, a better understanding of the role played by the immune system in modulat...
Source: Journal for Immunotherapy of Cancer - March 29, 2019 Category: Cancer & Oncology Source Type: research

Proteomic test for anti-PD-1 checkpoint blockade treatment of metastatic melanoma with and without BRAF mutations
AbstractThe therapeutic landscape in metastatic melanoma has changed dramatically in the last decade, with the success of immune checkpoint inhibitors resulting in durable responses for a large number of patients. For patients withBRAF mutations, combinations of BRAF and MEK inhibitors demonstrated response rates and benefit comparable to those from immune checkpoint inhibitors, providing the rationale for sequential treatment with targeted and immunotherapies and raising the question of optimal treatment sequencing.Biomarkers for the selection of anti-PD-1 therapy inBRAF wild type (BRAF WT) and inBRAF mutated (BRAF MUT) p...
Source: Journal for Immunotherapy of Cancer - March 29, 2019 Category: Cancer & Oncology Source Type: research

Lymphopenia in Cancer Patients and its Effects on Response to Immunotherapy: an opportunity for combination with Cytokines?
AbstractQuantitative lymphocyte alterations are frequent in patients with cancer, and strongly impact prognosis and survival. The development of cancers in immunosuppressed patients has demonstrated the contribution of different T cell populations, including CD4+ cells, in the control of cancer occurrence.Whereas absolute numbers of neutrophils, platelets and red blood cells are routinely monitored in clinic following treatments, because of possible short-term complications, absolute lymphocyte counts (ALC), their subpopulations or diversity (phenotype, TCR) are rarely analyzed and never used to choose therapy or as progno...
Source: Journal for Immunotherapy of Cancer - March 28, 2019 Category: Cancer & Oncology Source Type: research

Immune-enrichment of non-small cell lung cancer baseline biopsies for multiplex profiling define prognostic immune checkpoint combinations for patient stratification
ConclusionsIn this hypothesis-generating study, deepening our understanding of immune-checkpoint biology, comprehensive protein-protein interaction and pathway mapping revealed that redundant immune-checkpoint interactors associate with positive outcomes, providing new avenues for the deciphering of molecular mechanisms behind effects of immunotherapeutic agents targeting immune-checkpoints analyzed. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 28, 2019 Category: Cancer & Oncology Source Type: research

Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung cancer
AbstractBackgroundClinically-available biomarkers to identify the fraction of patients with small cell lung cancer (SCLC) who respond to immune-checkpoint inhibitors (ICIs) are lacking. High nonsynonymous tumor mutational burden (TMB), as assessed by whole exome sequencing, correlates with improved clinical outcomes for patients with SCLC treated with ICIs. Whether TMB as assessed by targeted next generation sequencing (NGS) is associated with improved efficacy of ICIs in patients with SCLC is currently unknown. Here we determined whether TMB by targeted NGS is associated with efficacy of ICIs in patients with SCLC.Methods...
Source: Journal for Immunotherapy of Cancer - March 28, 2019 Category: Cancer & Oncology Source Type: research

Overall survival by clinical risk category for high dose interleukin-2 (HD IL-2) treated patients with metastatic renal cell cancer (mRCC): data from the PROCLAIM SM registry
ConclusionsAmong mRCC patients treated with HD IL-2, all risk groups have median and 2-year survival consistent with recent reports of checkpoint or targeted therapies for mRCC. Favorable and intermediate risk (by IMDC) patients treated with HD IL-2 have longer OS compared with poor risk patients, with most durable OS observed in favorable risk patients. Favorable risk patients treated with HD IL-2 alone have a 2-year OS of 74%. These data continue to support a recommendation for HD IL-2 for patients with mRCC who meet eligibility criteria.Trial registrationPROCLAIM,NCT01415167 was registered with ClinicalTrials.gov on Aug...
Source: Journal for Immunotherapy of Cancer - March 27, 2019 Category: Cancer & Oncology Source Type: research

Checkpoint inhibition immunotherapy for advanced local and systemic conjunctival melanoma: a clinical case series
ConclusionsThis report suggests that systemic immunotherapy with or without topical interferon is effective in treatment of malignant melanoma of the conjunctiva. Therefore, it can be considered for patients with advanced local conjunctival melanoma, those who refuse orbital exenteration surgery and those with systemic metastasis. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 25, 2019 Category: Cancer & Oncology Source Type: research

Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy
ConclusionsWe provide novel insight into the mechanism of action of N-803 plus anti-PD-L1 combination and offer preclinical proof of concept supporting clinical use of N-803 in combination with checkpoint inhibitors, including for patients non- and/or minimally responsive to either monotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 21, 2019 Category: Cancer & Oncology Source Type: research

Phase 1/2 study of epacadostat in combination with ipilimumab in patients with unresectable or metastatic melanoma
ConclusionsWhen combined with ipilimumab, epacadostat ≤50 mg BID demonstrated clinical and pharmacologic activity and was generally well tolerated in patients with advanced melanoma.Trial registrationClinicalTrials.gov identifier,NCT01604889. Registration date, May 9, 2012, retrospectively registered. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 20, 2019 Category: Cancer & Oncology Source Type: research

A phase II clinical trial of adoptive transfer of haploidentical natural killer cells for consolidation therapy of pediatric acute myeloid leukemia
AbstractConsolidation therapies for children with intermediate- or high-risk acute myeloid leukemia (AML) are urgently needed to achieve higher cure rates while limiting therapy-related toxicities. We determined if adoptive transfer of natural killer (NK) cells from haploidentical killer immunoglobulin –like receptor (KIR)–human leukocyte antigen (HLA)-mismatched donors may prolong event-free survival in children with intermediate-risk AML who were in first complete remission after chemotherapy. Patients received cyclophosphamide (Day − 7), fludarabine (Days − 6 through − ...
Source: Journal for Immunotherapy of Cancer - March 20, 2019 Category: Cancer & Oncology Source Type: research

Interleukin-1 alpha increases anti-tumor efficacy of cetuximab in head and neck squamous cell carcinoma
ConclusionsAltogether, these results suggest that IL-1 α in combination with cetuximab can induce a T cell-dependent anti-tumor immune response and may represent a novel immunotherapeutic strategy for EGFR-positive HNSCCs. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 19, 2019 Category: Cancer & Oncology Source Type: research

HHLA2 in intrahepatic cholangiocarcinoma: an immune checkpoint with prognostic significance and wider expression compared with PD-L1
ConclusionsCompared with PD-L1, HHLA2 is more prevalent and possesses more explicit prognostic significance, which confer the rationale for HHLA2 as a potential immunotherapeutic target next to PD-L1 for ICC patients. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 18, 2019 Category: Cancer & Oncology Source Type: research

Merger of dynamic two-photon and phosphorescence lifetime microscopy reveals dependence of lymphocyte motility on oxygen in solid and hematological tumors
ConclusionsThis study demonstrates a versatile and highly contextual FaST-PLIM method for phosphorescence lifetime-based oxygen imaging in living animal tumor immunology models. The initial results of this method application to ALL and solid lung tumor models highlight the importance of oxygen supply for the maintenance of intratumoral T cell migration, define a 5  mmHg local oxygen concentration threshold for TIL motility, and demonstrate efficacy of supplementary oxygen breathing in TIL motility enhancement coincident with reduction of tumor hypoxia. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 18, 2019 Category: Cancer & Oncology Source Type: research

Correction to: A gene expression assay for simultaneous measurement of microsatellite instability and anti-tumor immune activity
. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 15, 2019 Category: Cancer & Oncology Source Type: research

Therapeutic efficacy, pharmacokinetic profiles, and toxicological activities of humanized antibody-drug conjugate Zt/g4-MMAE targeting RON receptor tyrosine kinase for cancer therapy
ConclusionsH-Zt/g4-MMAE is superior in eradication of pancreatic cancer xenografts with favorable pharmacokinetic profiles and manageable toxicological activities. These findings warrant the transition of H-Zt/g4-MMAE into clinical trials in the future. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 14, 2019 Category: Cancer & Oncology Source Type: research

Cocultures of human colorectal tumor spheroids with immune cells reveal the therapeutic potential of MICA/B and NKG2A targeting for cancer treatment
ConclusionsAltogether, we show that tumor spheroids represent a relevant tool to study tumor-lymphocyte interactions on human tissues and revealed the antitumor potential of immunomodulatory antibodies targeting MICA/B and NKG2A. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 14, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study
. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 14, 2019 Category: Cancer & Oncology Source Type: research

An interim report on the investigator-initiated phase 2 study of pembrolizumab immunological response evaluation (INSPIRE)
AbstractBackgroundImmune checkpoint inhibitors (ICIs) demonstrate unprecedented efficacy in multiple malignancies; however, the mechanisms of sensitivity and resistance are poorly understood and predictive biomarkers are scarce. INSPIRE is a phase 2 basket study to evaluate the genomic and immune landscapes of peripheral blood and tumors following pembrolizumab treatment.MethodsPatients with incurable, locally advanced or metastatic solid tumors that have progressed on standard therapy, or for whom no standard therapy exists or standard therapy was not deemed appropriate, received 200  mg pembrolizumab intravenously...
Source: Journal for Immunotherapy of Cancer - March 13, 2019 Category: Cancer & Oncology Source Type: research

Evaluating in vivo efficacy – toxicity profile of TEG001 in humanized mice xenografts against primary human AML disease and healthy hematopoietic cells
ConclusionWithin the limitations of humanized PD-X models, targeting CD277J by TEG001 is safe and efficient. Therefore, we have initiated clinical testing of TEG001 in a phase I first-in-human clinical trial (NTR6541; date of registration 25 July 2017). (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 12, 2019 Category: Cancer & Oncology Source Type: research

Antisense oligonucleotide targeting CD39 improves anti-tumor T cell immunity
ConclusionTargeting of CD39 by ASOs represents a promising state-of-the art therapeutic approach to improve immune responses against tumors. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 12, 2019 Category: Cancer & Oncology Source Type: research

Follicular lymphoma patients with KIR2DL2 and KIR3DL1 and their ligands (HLA-C1 and HLA-Bw4) show improved outcome when receiving rituximab
ConclusionsThe data presented here indicate that a subset of FL patients, identified by certain KIRs/KIR-ligands, have improved outcome and may benefit from additional rituximab treatment. Taken together, this suggests that the efficacy of tumor-reactive mAb treatment for some patients is influenced by KIRs on NK cells. However, prior to considering these genotypes in a clinically-actionable manner, these findings need independent validation in other studies. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 12, 2019 Category: Cancer & Oncology Source Type: research

Collagen density regulates the activity of tumor-infiltrating T cells
ConclusionsOur study identifies a new immune modulatory mechanism, which could be essential for suppression of T cell activity in the tumor microenvironment. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 12, 2019 Category: Cancer & Oncology Source Type: research

Perception of cure among patients with metastatic genitourinary cancer initiating immunotherapy
ConclusionThe current study found that a considerable proportion of patients with advanced GU cancers harbor inaccurate expectations concerning the potential benefit of immunotherapy. These results suggest that more effective counselling may mitigate patient anxiety, and potentially promote treatment satisfaction and adherence. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 12, 2019 Category: Cancer & Oncology Source Type: research

Complete response of renal cell carcinoma vena cava tumor thrombus to neoadjuvant immunotherapy
ConclusionsPreoperative immunotherapy with nivolumab and ipilimumab for locally advanced clear cell renal cancer resulted in a complete response of an extensive vena cava tumor thrombus, which enabled curative-intent resection of a non-responding primary tumor. If validated in larger cohorts, preoperative immunotherapy for locally advanced renal cell carcinoma may ultimately impact surgical planning and long-term prognosis. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 11, 2019 Category: Cancer & Oncology Source Type: research

Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC)
ConclusionsTaken together, our study indicate variable expression and clinical role of B7-family ligands in SCLC with predominant expression of the candidate target B7-H3 and the presence of a limited cytotoxic anti-tumor immune response. These results support the evaluation of B7-H3 blockers and/or pro-inflammatory therapies in SCLC. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 8, 2019 Category: Cancer & Oncology Source Type: research

Correction to: persistent mutant oncogene specific T cells in two patients benefitting from anti-PD-1
. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 6, 2019 Category: Cancer & Oncology Source Type: research

Radiotherapy enhances responses of lung cancer to CTLA-4 blockade
AbstractFormenti et al. have recently reported the clinical outcomes and translational readouts of a trial of the anti-CTLA-4 inhibitor, ipilimumab, in combination with palliative radiotherapy in 39 patients with non-small cell lung cancer. A radiological response was seen in 18% of patients and 31% of patients experienced disease control. These clinical outcomes appear to be superior to historical studies using ipilimumab alone and suggest that radiation may have triggered systemic, so-called abscopal, immune responses in some patients. Induction of interferon-beta (IFN- β) and maximal expansion and contraction of di...
Source: Journal for Immunotherapy of Cancer - March 6, 2019 Category: Cancer & Oncology Source Type: research

α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas
ConclusionsWe show that α-PD-1 not only initiates a tumor rejection program, but can induce a competing TGFβ-driven immuno-suppressive program. We identify new opportunities for α-PD-1/α-TGFβ combinatorial treatment of SCCs especially those with a high mutation load, high CD4+ T cell content and pSmad3 signaling. Our data form the basis for clinical trial of α-TGFβ/α-PD-1 combination therapy (NCT02947165). (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 4, 2019 Category: Cancer & Oncology Source Type: research

Exceptional response and multisystem autoimmune-like toxicities associated with the same T cell clone in a patient with uveal melanoma treated with immune checkpoint inhibitors
AbstractBalancing the potential for durable remissions with autoimmune-like toxicities is a key clinical challenge in the use of immune checkpoint inhibitors (ICI). Certain toxicities are associated with an increased response rate; however, the molecular underpinnings of this association are poorly understood. Here, we report a patient with wide spread uveal melanoma who had an exceptional response to treatment with ipilimumab and nivolumab, but suffered severe immune-related sequelae, including central serous retinopathy with retinal detachment, tinnitus, and vitiligo resembling Vogt-Koyanagi-Harada disease, and refractor...
Source: Journal for Immunotherapy of Cancer - March 4, 2019 Category: Cancer & Oncology Source Type: research

A novel TLR4 binding protein, 40S ribosomal protein S3, has potential utility as an adjuvant in a dendritic cell-based vaccine
ConclusionsThis study therefore proved that human cancer cell-derived RPS3, a novel TLR4 ligand, has great potential as an adjuvant in tumor-specific antigen DC-based vaccines. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - February 28, 2019 Category: Cancer & Oncology Source Type: research