The expression of MHC class II molecules on murine breast tumors delays T-cell exhaustion, expands the T-cell repertoire, and slows tumor growth
AbstractThe expression of MHC class II molecules (MHCII) on tumor cells correlates with survival and responsiveness to immunotherapy. However, the mechanisms underlying these observations are poorly defined. Using a murine breast tumor line, we showed that MHCII-expressing tumors grew more slowly than controls and recruited more functional CD4+ and CD8+ T cells. In addition, MHCII-expressing tumors contained more TCR clonotypes expanded to a larger degree than control tumors. Functional CD8+ T cells in tumors depended on CD4+ T cells. However, both CD4+ and CD8+ T cells eventually became exhausted, even in MHCII-expressing...
Source: Cancer Immunology, Immunotherapy - October 17, 2018 Category: Cancer & Oncology Source Type: research

Histamine targets myeloid-derived suppressor cells and improves the anti-tumor efficacy of PD-1/PD-L1 checkpoint blockade
AbstractMyeloid-derived suppressor cells (MDSCs) are immature monocytes and granulocytes that impede immune-mediated clearance of malignant cells by multiple mechanisms, including the formation of immunosuppressive reactive oxygen species (ROS) via the myeloid cell NADPH oxidase (NOX2). Histamine dihydrochloride (HDC), a NOX2 inhibitor, exerts anti-cancer efficacy in experimental tumor models but the detailed mechanisms are insufficiently understood. To determine effects of HDC on the MDSC compartment we utilized three murine cancer models known to entail accumulation of MDSC, i.e. EL-4 lymphoma, MC-38 colorectal carcinoma...
Source: Cancer Immunology, Immunotherapy - October 12, 2018 Category: Cancer & Oncology Source Type: research

Association of IL-36 γ with tertiary lymphoid structures and inflammatory immune infiltrates in human colorectal cancer
AbstractIL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36 γ is an IL-1 family cytokine involved in polarizing type-1 immune responses. However, its function in the gut, including in colorectal cancer pathogenesis, is not well appreciated. In a murine model of colon carcinoma, IL-36γ controls tertiary lymphoid structure formation and promotes a type-1 imm une response concurrently with a decrease in expression of immune checkpoint molecules in the tumor microenvironment. Here, we demonstrate that IL-36γ plays a simil...
Source: Cancer Immunology, Immunotherapy - October 12, 2018 Category: Cancer & Oncology Source Type: research

Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study
In conclusion, our results suggest that high sCTLA-4 serum levels might predict favorable clinical outcome and higher risk of irAEs in IPI-treated MM patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 11, 2018 Category: Cancer & Oncology Source Type: research

Recurrent grade 4 panuveitis with serous retinal detachment related to nivolumab treatment in a patient with metastatic renal cell carcinoma
AbstractBlockade of programmed cell death-1 (PD-1) has become one of the most promising immunotherapies for many human cancers. However, immune-related adverse events can be produced by anti-PD-1 therapy. Uveitis is a rare but potentially devastating side effect of anti-PD-1 therapy. Delay in diagnosis or improper treatment may eventually lead to irreversible blindness. Therefore, it is important for the oncologist and the ophthalmologist to recognize and manage this adverse event properly in patients receiving anti-PD-1 therapy in a timely manner. Here we present a grade 4 panuveitis with bilateral serous retinal detachme...
Source: Cancer Immunology, Immunotherapy - October 11, 2018 Category: Cancer & Oncology Source Type: research

Phase I/II clinical trial of a Wilms ’ tumor 1-targeted dendritic cell vaccination-based immunotherapy in patients with advanced cancer
AbstractDendritic cell (DC)-based immunotherapies have been created for a broad expanse of cancers, and DC vaccines prepared with Wilms ’ tumor protein 1 (WT1) peptides have shown great therapeutic efficacy in these diseases. In this paper, we report the results of a phase I/II study of a DC-based vaccination for advanced breast, ovarian, and gastric cancers, and we offer evidence that patients can be effectively vaccinated with a utologous DCs pulsed with WT1 peptide. There were ten patients who took part in this clinical study; they were treated biweekly with a WT1 peptide-pulsed DC vaccination, with toxicity and c...
Source: Cancer Immunology, Immunotherapy - October 10, 2018 Category: Cancer & Oncology Source Type: research

Opposing roles of eosinophils in cancer
AbstractEosinophils are a subset of granulocytes mostly known for their ability to combat parasites and induce allergy. Although they were described to be related to cancer more than 100  years ago, their role in tumors is still undefined. Recent observations revealed that they display regulatory functions towards other immune cell subsets in the tumor microenvironment or direct cytotoxic functions against tumor cells, leading to either antitumor or protumor effects. This paradoxic al role of eosinophils was suggested to be dependent on the different factors in the TME. In addition, the clinical relevance of these cel...
Source: Cancer Immunology, Immunotherapy - October 9, 2018 Category: Cancer & Oncology Source Type: research

Prediction of neoepitopes from murine sequencing data
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 5, 2018 Category: Cancer & Oncology Source Type: research

An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells
AbstractBreast cancer remains one of the leading causes of cancer-associated death worldwide. Conventional treatment is associated with substantial toxicity and suboptimal efficacy. We, therefore, developed and evaluated the in vitro efficacy of an autologous dendritic cell (DC) vaccine to treat breast cancer. We recruited 12 female patients with stage 1, 2, or 3 breast cancer and matured their DCs with autologous tumour-specific lysate, a toll-like receptor (TLR)-3 and 7/8 agonist, and an interferon-containing cocktail. The efficacy of the vaccine was evaluated by its ability to elicit a cytotoxic T-lymphocyte response to...
Source: Cancer Immunology, Immunotherapy - October 3, 2018 Category: Cancer & Oncology Source Type: research

Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics
AbstractBreast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23 α, miR-146α, miR-155 and miR-181α), in opera...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Epidermal growth factor receptor peptide vaccination induces cross-reactive immunity to human EGFR, HER2, and HER3
AbstractCurrent treatments for tumors expressing epidermal growth factor receptor (EGFR) include anti-EGFR monoclonal antibodies, often used in conjunction with the standard chemotherapy, radiation therapy, or other EGFR inhibitors. While monoclonal antibody treatment is efficacious in many patients, drawbacks include its high cost of treatment and side effects associated with multiple drug infusions. As an alternative to monoclonal antibody treatments, we have focused on peptide-based vaccination to trigger natural anti-tumor antibodies. Here, we demonstrate that peptides based on a region of the EGFR extracellular domain...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia
AbstractIn elderly acute myeloid leukemia (AML) patients post-remission treatment options are associated with high comorbidity rates and poor survival. Dendritic cell (DC)-based immunotherapy is a promising alternative treatment strategy. A novel allogeneic DC vaccine, DCP-001, was developed from an AML-derived cell line that uniquely combines the positive features of allogeneic DC vaccines and expression of multi-leukemia-associated antigens. Here, we present data from a phase I study conducted with DCP-001 in 12 advanced-stage elderly AML patients. Patients enrolled were in complete remission (CR1/CR2) (n =&thinsp...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Fusobacterium nucleatum promotes M2 polarization of macrophages in the microenvironment of colorectal tumours via a TLR4-dependent mechanism
AbstractFusobacterium nucleatum (Fn) has been shown to promote colorectal cancer (CRC) development by inhibiting host anti-tumour immunity. However, the impact ofFn infection on macrophage polarization and subsequent intestinal tumour formation as well as the underlying molecular pathways has not been investigated. We investigated the impact ofFn infection on macrophage polarization in human CRCs and cultured macrophages as well as the effects on macrophage phenotype and intestinal tumour formation inApcMin/+ mice. We also examined whether macrophage-polarized activation challenged byFn infection via a TLR4-dependent mecha...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Increased antitumor activities of glypican-3-specific chimeric antigen receptor-modified T cells by coexpression of a soluble PD1 –CH3 fusion protein
AbstractOur recent clinical study demonstrated that glypican-3 (GPC3)-specific chimeric antigen receptor-modified T (CAR-T) cells are a promising treatment for hepatocellular carcinoma (HCC). However, the interaction of programmed cell death 1 (PD-1) and PD-L1-mediated T-cell inhibition is involved in immune evasion in a wide range of solid tumors, including HCC. To overcome this problem, we introduced a fusion protein composed of a PD-1 extracellular domain and CH3 from IgG4 into GPC3-specific CAR-T cells (GPC3-28Z) to block the PD-1/PD-L1 pathway. GPC3-specific CAR-T cells carrying the PD-1 –CH3 fusion protein (sPD...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

High-grade glioma associated immunosuppression does not prevent immune responses induced by therapeutic vaccines in combination with T reg depletion
AbstractHigh-grade gliomas (HGG) exert systemic immunosuppression, which is of particular importance as immunotherapeutic strategies such as therapeutic vaccines are increasingly used to treat HGGs. In a first cohort of 61 HGG patients we evaluated a panel of 30 hematological and 34 plasma biomarkers. Then, we investigated in a second cohort of 11 relapsed HGG patients receiving immunomodulation with metronomic cyclophosphamide upfront to a DC-based vaccine whether immune abnormalities persisted and whether they hampered induction of IFN γ+ T-cell responses. HGG patients from the first cohort showed increased numbers...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma
AbstractPhase I testing of the hu14.18-IL2 immunocytokine (IC) in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5  mg/m2/day. Preclinical data in IC-treated tumor-bearing mice with low tumor burden documented striking antitumor effects. Patients with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 courses of IC at 6  mg/m2/day i.v. on days 1, 2 and 3 of each 28-day course. Patients were randomized to complete surgical resection either following neoadjuvant (Group A) or prior to adjuvant (Group B) IC course 1. Primary...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

3-Day monocyte-derived dendritic cells stimulated with a combination of OK432, TLR7/8 ligand, and prostaglandin E 2 are a promising alternative for cancer immunotherapy
In conclusion, the OK432 cocktail has the advantage of inducing IL-12p70 production without impairing phenotype or T-cell stimulatory capacity of the cells and might, therefore, be an advantageous alternative to be used in DC-based immunotherapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Ex vivo expanded tumour-infiltrating lymphocytes from ovarian cancer patients release anti-tumour cytokines in response to autologous primary ovarian cancer cells
AbstractEpithelial ovarian cancer (EOC) is the leading cause of gynaecological cancer-related death in Europe. Although most patients achieve an initial complete response with first-line treatment, recurrence occurs in more than 80% of cases. Thus, there is a clear unmet need for novel second-line treatments. EOC is frequently infiltrated with T lymphocytes, the presence of which has been shown to be associated with improved clinical outcomes. Adoptive T-cell therapy (ACT) using ex vivo-expanded tumour-infiltrating lymphocytes (TILs) has shown remarkable efficacy in other immunogenic tumours, and may represent a promising ...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics
AbstractBreast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23 α, miR-146α, miR-155 and miR-181α), in opera...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Absence of host NF- κB p50 induces murine glioblastoma tumor regression, increases survival, and decreases T-cell induction of tumor-associated macrophage M2 polarization
AbstractHigh-grade gliomas harbor abundant myeloid cells that suppress anti-tumor immunity and support tumor growth. Targeting transcription factors, such as NF- κB p50, that mediate suppressive myeloid M2 polarization may prove therapeutic. GL261-Luc glioblastoma cells were inoculated into wild-type and p50−/− mice, followed by analysis of tumor growth, survival, tumor myeloid cells, and T cells. The absence of host p50 slows tumor growth and enables regression in 30% of recipients, leading to prolonged survival. Tumors developing in p50−/− mice possess a greater concentration of tumor-infilt...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Regulatory mechanisms of PD-L1 expression in cancer cells
AbstractImmunotherapy targeting the PD-L1/PD-1 pathway using antibodies is effective in the clinical treatment of a multitude of cancers. This makes research of the regulatory mechanisms of PD-1 expression in cancer cells intriguing. PD-L1 expression can be categorized into inducible expression, attributed to extrinsic factors in the microenvironment, and constitutive expression, attributed to intrinsic cancer-driving gene alteration. The mechanisms of PD-L1 expression in cancer cells operate at multiple levels, including gene amplification, chromatin modification, transcription, posttranscription, translation and posttran...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Antitumor virotherapy using syngeneic or allogeneic mesenchymal stem cell carriers induces systemic immune response and intratumoral leukocyte infiltration in mice
In this study we use our virotherapy Celyvir with syngeneic and allogeneic mouse mesenchymal stem cells to determine their antitumor efficacy in a C57BL/6 murine adenocarcinoma model. Adoptive transfer of splenocytes from treated mice to new tumor-bearing mice followed by a secondary adoptive transfer to a third group was performed. Similar reduction of tumor growth and systemic activation of the innate and adaptive immune system was observed in groups treated with syngeneic or allogeneic mesenchymal stem cells loaded with ICOVIR-5. Moreover, a different pattern of infiltration was observed by immunofluorescence in Celyvir...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma
In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8+ and CD4+ T cells secreting interferon-(IFN)-...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Case report: Long-term survival of a pancreatic cancer patient immunized with an SVN-2B peptide vaccine
AbstractA 62-year-old woman who underwent surgery to treat pancreatic cancer provided written, informed consent to undergo adjuvant therapy with gemcitabine, tegafur, and uracil. However, this was stopped after only 14  days due to Grade 4 neutropenia. She was then started on vaccine therapy with Survivin 2B peptide (SVN-2B) including IFA and INF-α. Although metastatic lung tumors were identified and resected at 82 months after surgery, the patient has remained free of new or relapsed disease for 12 years ther eafter. Tetramer and ELISPOT assays revealed the continuous circulation of SVN-2B-restricted ...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells
AbstractCholangiocarcinoma (CCA) is a cancer of the bile ducts that is associated with poor prognosis and poor treatment outcome. Approximately one-third of CCA patients can undergo surgery, but the recurrence rate is high and chemotherapy often cannot satisfactorily prolong survival. Cellular immunotherapy based on adoptive T-cell transfer is a potential treatment for CCA; however, the development of this technology and the search for an appropriate tumor-associated antigen are still ongoing. To enhance the cytotoxic activity of effector T cells against CCA, we developed self-differentiated monocyte-derived dendritic cell...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study
ConclusionsOur study suggests that immunotherapy is effective and well tolerated in the elderly. The PFS on pembrolizumab was greater than expected, a finding that needs to be investigated further. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

CD19 + tumor-infiltrating B-cells prime CD4 + T-cell immunity and predict platinum-based chemotherapy efficacy in muscle-invasive bladder cancer
ConclusionCD19+ TIB was identified as an independent prognostic factor, which could predict for post-surgery survival and platinum-based ACT benefits in MIBC. CD19+ TIB serve as antigen-presenting cells (APCs) to activate CD4+ TIT in the tumor environment of MIBC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 26, 2018 Category: Cancer & Oncology Source Type: research

TRPM2 modulates neutrophil attraction to murine tumor cells by regulating CXCL2 expression
AbstractIn recent years, immune cells were shown to play critical roles in tumor growth and metastatic progression. In this context, neutrophils were shown to possess both pro- and anti-tumor properties. To exert their anti-tumor effect, neutrophils need to migrate towards, and form physical contact with tumor cells. Neutrophils secrete H2O2 in a contact-dependent mechanism, thereby inducing a lethal Ca2+ influx via the activation of the H2O2-dependent TRPM2 Ca2+ channel. Here, we explored the mechanism regulating neutrophil chemoattraction to tumor cells. Interestingly, we found that TRPM2 plays a role in this context as ...
Source: Cancer Immunology, Immunotherapy - September 24, 2018 Category: Cancer & Oncology Source Type: research

The role of CCR5 in directing the mobilization and biological function of CD11b + Gr1 + Ly6C low polymorphonuclear myeloid cells in cancer
AbstractBone marrow (BM) cells of the hematopoietic system, also known as BM-derived leukocytes (BMD), are mobilized from the BM to the blood and then colonize tumor sites. These cells then become key players in either promoting or regulating the development and progression of tumors. Among the cells that suppress anti-tumor immunity are regulatory T cells (Tregs), tumor-associated macrophages (TAMS) and myeloid-derived suppressor cells (MDSC). MDSC comprise CD11b+Gr1+Ly6Clow polymorphonuclear myeloid cells (PMN-MDSC), and CD11b+Gr1+Ly6Chigh monocytic myeloid cells (Mo-MDSC). Several studies including ours have identified ...
Source: Cancer Immunology, Immunotherapy - September 19, 2018 Category: Cancer & Oncology Source Type: research

TIGIT: a novel immunotherapy target moving from bench to bedside
AbstractTreatment strategies for patients with advanced solid tumors have traditionally been based on three different paradigms: surgery, cytotoxics (chemotherapy or radiation therapy) and targeted therapies. Immunotherapy has emerged as a novel treatment paradigm in our armamentarium. Unfortunately, most patients still do not benefit from immunotherapy. These patients often have “cold tumors” characterized by a paucity of effector T cells in the tumor microenvironment, low mutational load, low neoantigen burden and often an immunosuppressive tumor microenvironment. TIGIT is an immunoreceptor inhibitory checkpo...
Source: Cancer Immunology, Immunotherapy - September 19, 2018 Category: Cancer & Oncology Source Type: research

The role of CCR5 in directing the mobilization and biological function of CD11b + Gr1 + Ly6C low polymorphonuclear myeloid cells in cancer
AbstractBone marrow (BM) cells of the hematopoietic system, also known as BM-derived leukocytes (BMD), are mobilized from the BM to the blood and then colonize tumor sites. These cells then become key players in either promoting or regulating the development and progression of tumors. Among the cells that suppress anti-tumor immunity are regulatory T cells (Tregs), tumor-associated macrophages (TAMS) and myeloid-derived suppressor cells (MDSC). MDSC comprise CD11b+Gr1+Ly6Clow polymorphonuclear myeloid cells (PMN-MDSC), and CD11b+Gr1+Ly6Chigh monocytic myeloid cells (Mo-MDSC). Several studies including ours have identified ...
Source: Cancer Immunology, Immunotherapy - September 19, 2018 Category: Cancer & Oncology Source Type: research

Sustained efficacy of adjuvant immunotherapy with cytokine-induced killer cells for hepatocellular carcinoma: an extended 5-year follow-up
AbstractOur earlier multicenter randomized controlled trial showed that adjuvant immunotherapy with cytokine-induced killer (CIK) cells resulted in longer recurrence-free survival (RFS) and overall survival (OS) as well in patients who received curative treatment for hepatocellular carcinoma (HCC). In the present study, we determined if the efficacy of CIK cell therapy continued after end of repeated CIK cell injections. We performed a follow-up study of our preceding trial. We included 226 patients: 114 patients in the immunotherapy group (injection of 6.4  × 109 CIK cells, 16 times during 60 weeks) an...
Source: Cancer Immunology, Immunotherapy - September 19, 2018 Category: Cancer & Oncology Source Type: research

β-Adrenergic signaling blocks murine CD8 + T-cell metabolic reprogramming during activation: a mechanism for immunosuppression by adrenergic stress
This study demonstrates that one mechanism by which β2-AR signaling can inhibit CD8+ T-cell activation  is by suppressing the required metabolic reprogramming events which accompany activation of these immune cells and thus reveals a new mechanism by which adrenergic stress can suppress the effector activity of immune cells. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 18, 2018 Category: Cancer & Oncology Source Type: research

Accurate quantification of T-cells expressing PD-1 in patients on anti-PD-1 immunotherapy
AbstractIncreasing numbers of trials employing anti-PD-1 immunotherapy emphasize the requirement for predictive biomarkers of clinical response. Many studies examine the cell surface expression of PD-1 and other key regulators of T-cell activation and inhibition. Here, we compared common commercially available anti-PD-1 diagnostic antibodies and tested whether they can bind the PD-1 receptor in the presence of the therapeutic antagonists pembrolizumab and nivolumab. We observed that currently no antibodies are available that can reliably stain all PD-1 receptors on T-cells from patients treated with anti-PD-1 antibodies. F...
Source: Cancer Immunology, Immunotherapy - September 14, 2018 Category: Cancer & Oncology Source Type: research

A phase I/randomized phase II study of GM.CD40L vaccine in combination with CCL21 in patients with advanced lung adenocarcinoma
AbstractThe GM.CD40L vaccine, which recruits and activates dendritic cells, migrates to lymph nodes, activating T cells and leading to systemic tumor cell killing. When combined with the CCL21 chemokine, which recruits T cells and enhances T-cell responses, additive effects have been demonstrated in non-small cell lung cancer mouse models. Here, we compared GM.CD40L versus GM.CD40L plus CCL21 (GM.CD40L.CCL21) in lung adenocarcinoma patients with ≥ 1 line of treatment. In this phase I/II randomized trial (NCT01433172), patients received intradermal vaccines every 14 days (3 doses) and then monthly (3 doses). A two...
Source: Cancer Immunology, Immunotherapy - September 12, 2018 Category: Cancer & Oncology Source Type: research

Oncogenic MYD88 mutations in lymphoma: novel insights and therapeutic possibilities
AbstractOncogenicMYD88 mutations, most notably the Leu 265 Pro (L265P) mutation, were recently identified as potential driver mutations in various B-cell non-Hodgkin Lymphomas (NHLs). The L265P mutation is now thought to be common to virtually all NHLs and occurs in between 4 and 90% of cases, depending on the entity. Since it is tumor-specific, the mutation, and the pathways it regulates, might serve as advantageous therapeutic targets for both conventional chemotherapeutic intervention, as well as immunotherapeutic strategies. Here, we review recent progress on elucidating the molecular and cellular processes affected by...
Source: Cancer Immunology, Immunotherapy - September 11, 2018 Category: Cancer & Oncology Source Type: research

Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies
AbstractBackgroundImmune checkpoint blockade (ICB) and BRAFV600-targeted therapy have demonstrated substantial clinical efficacy for patients with stage 4 melanoma in clinical trials; however, their impact on survival and barriers to treatment in the “real-life” setting remains unknown.MethodsPatients who presented with cutaneous melanoma during 2004 –2015 using the National Cancer Database, which comprises >  70% of all newly diagnosed cancers in the U.S., were evaluated for predictors of presenting with stage 4 disease and receiving ICB, and for their associated unadjusted and risk...
Source: Cancer Immunology, Immunotherapy - September 6, 2018 Category: Cancer & Oncology Source Type: research

International Symposium: Trailblazing in Cancer Immunotherapy, October 29 –31, 2017, Pamplona, Spain
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 4, 2018 Category: Cancer & Oncology Source Type: research

Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC)
ConclusionIn conclusion, the efficacy of immunotherapy is dependent on the metastatic location. Treatment appears more active in lymph nodes compared to other organ sites such as liver, adrenals and bone. Future strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 31, 2018 Category: Cancer & Oncology Source Type: research

TCR repertoire profiling of tumors, adjacent normal tissues, and peripheral blood predicts survival in nasopharyngeal carcinoma
In conclusion, we here report the systematic and overall characteristics of the TCR repertoire in tumors, adjacent normal tissues, and peripheral blood of NPC patients. The data obtained may be relevant to future clini cal studies in the setting of immunotherapy for NPC patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 28, 2018 Category: Cancer & Oncology Source Type: research

Chemotherapy-induced apoptosis, autophagy and cell cycle arrest are key drivers of synergy in chemo-immunotherapy of epithelial ovarian cancer
In conclusion, the mechanism driving synergy in chemo-immunotherapy of EOC is multifactorial. A deeper understanding of such process is needed to better design combination therapies and carefully stratify patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 24, 2018 Category: Cancer & Oncology Source Type: research

Beta-glucan-induced inflammatory monocytes mediate antitumor efficacy in the murine lung
Abstractβ-Glucan is a naturally occurring glucose polysaccharide with immunostimulatory activity in both infection and malignancy. β-Glucan’s antitumor effects have been attributed to the enhancement of complement receptor 3-dependent cellular cytotoxicity, as well as modulation of suppressive and stimu latory myeloid subsets, which in turn enhances antitumor T cell immunity. In the present study, we demonstrate antitumor efficacy of yeast-derived β-glucan particles (YGP) in a model of metastatic-like melanoma in the lung, through a mechanism that is independent of previously reported β-glucan-me ...
Source: Cancer Immunology, Immunotherapy - August 23, 2018 Category: Cancer & Oncology Source Type: research

Anergic natural killer cells educated by tumor cells are associated with a poor prognosis in patients with advanced pancreatic ductal adenocarcinoma
This study was performed to determine the unique subtype of “educated” NK cells and their prognostic value in patients with advanced pancreatic cancer.MethodsWe divided 378 eligible patients into a derivation cohort (September 2010 to December 2014,n = 239) and a validation cohort (January 2015 to April 2016,n = 139). Flow cytometry was performed to analyze NK cells. Enzyme-linked immunosorbent assay was used to detect interleukin-2 (IL-2), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. The Kaplan–Meier method and the Cox proportional h...
Source: Cancer Immunology, Immunotherapy - August 22, 2018 Category: Cancer & Oncology Source Type: research

Circulating CD8 + T-cell repertoires reveal the biological characteristics of tumors and clinical responses to chemotherapy in breast cancer patients
ConclusionsAlthough functional studies of clonally expanded CD8+ T-cell populations are clearly required, our results suggest that the circulating CD8+ T-cell repertoire reflects the characteristics of the tumor-associated biomolecules released into the blood and correlates with the clinical responses of the patients to chemotherapy which might assist in making treatment decisions. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 22, 2018 Category: Cancer & Oncology Source Type: research

T cell receptor sequencing of activated CD8 T cells in the blood identifies tumor-infiltrating clones that expand after PD-1 therapy and radiation in a melanoma patient
In this study, we utilized TCR sequencing to dissect the composition of peripheral blood CD8 T cells activated upon therapy, comparing it with tumor-infiltrating lymphocytes. We report on a nonagenarian melanoma patient who showed a prominent increase in peripheral blood Ki-67  + CD8 T cells following brain stereotactic radiation and anti-PD-1 immunotherapy. Proliferating CD8 T cells exhibited an effector-like phenotype with expression of CD38, HLA-DR and Granzyme B, as well as expression of the positive costimulatory molecules CD28 and CD27. TCR sequencing of periphe ral blood CD8 T cells revealed a highly o...
Source: Cancer Immunology, Immunotherapy - August 22, 2018 Category: Cancer & Oncology Source Type: research

Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial
AbstractDendritic cell (DC)-based vaccination is a promising approach for active-specific immunotherapy, but is currently of limited efficacy. The safety and effectiveness of a DC vaccine (DCV) loaded with glioblastoma stem cell-like (GSC) antigens was assessed in glioblastoma multiforme (GBM) patients. In this double-blind, placebo-controlled phase II clinical trial, 43 GBM patients were randomized after surgery at a 1:1 ratio to receive either DCV (n = 22) or normal saline placebo (n = 21). Overall survival (OS) and progression-free survival (PFS) were analysed. Participants were stratified in...
Source: Cancer Immunology, Immunotherapy - August 22, 2018 Category: Cancer & Oncology Source Type: research

Determination of optimum vitamin D3 levels for NK cell-mediated rituximab- and obinutuzumab-dependent cellular cytotoxicity
AbstractVitamin D3 (25-OH-D3) deficiency impairs rituximab-dependent cellular cytotoxicity and the outcome of patients with diffuse large B-cell and follicular lymphomas (DLBCL). Since the optimum 25-OH-D3 serum levels for NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) are unknown, we determined the 25-OH-D3 serum levels associated with maximum NK cell-mediated ADCC. CD20 antibody-loaded CD20+ B-cell lymphoma cell lines were cultured with NK cells and ADCC activity was determined by lactate dehydrogenase release assays. Using a newly developed formula, pre-defined 25-OH-D3 serum levels were achieved with ...
Source: Cancer Immunology, Immunotherapy - August 21, 2018 Category: Cancer & Oncology Source Type: research