Journal for ImmunoTherapy of Cancer

http://www.immunotherapyofcancer.org/

List of Papers (Total 1,372)

Interstitial nephritis in melanoma patients secondary to PD-1 checkpoint inhibitor

Background Immune checkpoint inhibitors have become the first line therapy in melanoma treatment and their use is extending to other malignancies. However, we are still learning about immune side effects produced by these drugs and their severity especially in patients with history of inflammatory diseases. Case presentation We present two cases of metastatic melanoma treated...

Radiotherapy and MVA-MUC1-IL-2 vaccine act synergistically for inducing specific immunity to MUC-1 tumor antigen

Background We previously demonstrated that tumor irradiation potentiates cancer vaccines using genetic modification of tumor cells in murine tumor models. To investigate whether tumor irradiation augments the immune response to MUC1 tumor antigen, we have tested the efficacy of tumor irradiation combined with an MVA-MUC1-IL2 cancer vaccine (Transgene TG4010) for murine renal...

Unfolding anti-tumor immunity: ER stress responses sculpt tolerogenic myeloid cells in cancer

Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of...

Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma

Background Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR...

Potassium channels of T lymphocytes take center stage in the fight against cancer

A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K + homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment (TME) suppress the function of effector T cells. Furthermore, they establish that overexpression of K + channels in T lymphocytes counterbalances this negative effect...

Challenges and opportunities for checkpoint blockade in T-cell lymphoproliferative disorders

The T-cell lymphoproliferative disorders are a heterogeneous group of non-Hodgkin’s lymphomas (NHL) for which current therapeutic strategies are inadequate, as most patients afflicted with these NHL will succumb to disease progression within 2 years of diagnosis. Appreciation of the genetic and immunologic landscape of these aggressive NHL, including PD-L1 (B7-H1, CD274...

Fusion of the dendritic cell-targeting chemokine MIP3α to melanoma antigen Gp100 in a therapeutic DNA vaccine significantly enhances immunogenicity and survival in a mouse melanoma model

Background Although therapeutic cancer vaccines have been mostly disappointing in the clinic, the advent of novel immunotherapies and the future promise of neoantigen-based therapies have created the need for new vaccine modalities that can easily adapt to current and future developments in cancer immunotherapy. One such novel platform is a DNA vaccine fusing the chemokine...

Being “penny-wise but pound foolish” in cancer immunotherapy research: the urgent need for mouse cancer models to reflect human modifying factors

Inbred mice are the mainstay for preclinical cancer assessment of potential therapeutics, especially immune-based approaches. However, the use of young, lean, inbred mice housed under specific-pathogen-free conditions does not mirror the human cancer scenario. This commentary discusses some of the issues in evaluating immunotherapeutics in mice given recent advances.

A New VISTA on combination therapy for negative checkpoint regulator blockade

Negative checkpoint regulators function to restrain T cell responses to maintain tolerance and limit immunopathology. However, in the setting of malignancy, these pathways work in concert to promote immune-mediate escape leading to the development of a clinically overt cancer. In the recent years, clinical trials demonstrating the efficacy of blocking antibodies against these...

Advances in immunotherapeutic strategies for colorectal cancer commentary on: tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients by Halama et al

Colorectal cancer is a leading cause of cancer-related death in the United States, despite recent advances in treatment strategies. The immune system has been implicated in the pathogenesis of colorectal cancer, with numerous studies identifying either antagonistic or pro-tumorigenic effects of infiltrating immune cells. Therapeutic strategies harnessing the immune system to...

Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy

Background Checkpoint inhibitor immunotherapy is becoming an effective treatment modality for an increasing number of malignancies. As a result, autoinflammatory side-effects are also being observed more commonly in the clinic. We are currently unable to predict which patients will develop more severe toxicities associated with these treatment regimens. Case presentation We...

Sarcoidosis in the setting of combination ipilimumab and nivolumab immunotherapy: a case report & review of the literature

Background We report a case of sarcoidosis in a patient with metastatic melanoma managed with combination ipilimumab/nivolumab. Sarcoid development has been linked with single agent immunotherapy but, to our knowledge, it has not been reported with combination ipilimumab/nivolumab treatment. This case raises unique management challenges for both the melanoma and the immunotherapy...

Immune-related response assessment during PD-1 inhibitor therapy in advanced non-small-cell lung cancer patients

Background Tumor response characteristics using immune-related RECIST1.1 (irRECIST1.1) in advanced non-small-cell lung cancer (NSCLC) patients treated with nivolumab monotherapy in the clinical setting have not been previously described with a direct comparison with the assessments according to the conventional RECIST1.1. Methods Fifty-six advanced NSCLC patients treated with...

A phase IB study of ipilimumab with peginterferon alfa-2b in patients with unresectable melanoma

Background Ipilimumab and peginterferon alfa-2b are established systemic treatment options for melanoma that have distinct mechanisms of action. Given the need for improved therapies for advanced melanoma, we conducted an open-label, single institution, phase Ib study to assess the safety and tolerability of using these two agents in combination. Methods Study treatment consisted...

Canine cancer immunotherapy studies: linking mouse and human

Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will respond and who will experience at times significant toxicities. Although advances in cancer immunotherapy depend on preclinical testing, the...

Validation of biomarkers to predict response to immunotherapy in cancer: Volume II — clinical validation and regulatory considerations

There is growing recognition that immunotherapy is likely to significantly improve health outcomes for cancer patients in the coming years. Currently, while a subset of patients experience substantial clinical benefit in response to different immunotherapeutic approaches, the majority of patients do not but are still exposed to the significant drug toxicities. Therefore, a...

Recurrent pleural effusions and cardiac tamponade as possible manifestations of pseudoprogression associated with nivolumab therapy– a report of two cases

Background Checkpoint inhibitors are a class of agents that employ host’s adaptive immune defenses in fighting cancer. With many new indications and several ongoing clinical trials in a variety of malignancies, the usage of these agents is set to increase significantly. One of the key challenges patients and physicians face while using these drugs is with the appropriate...

Unraveling the role of preexisting immunity in prostate cancer patients vaccinated with a HER-2/neu hybrid peptide

Background Cancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported on the levels of preexisting immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide (AE37), during a phase I clinical trial. The purpose of the current...

Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of renal cell carcinoma

Immunotherapy has produced durable clinical benefit in patients with metastatic renal cell cancer (RCC). In the past, patients treated with interferon-alpha (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which have lasted for multiple decades. More recently, a large number of new agents have been approved for RCC, several of which attack tumor...

Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810

Background Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) share exposure to UV light as the dominant risk factor, and these tumors therefore harbor high mutation burdens. In other malignancies, high mutation burden has been associated with clinical benefit from therapy with antibodies directed against the Programmed Death 1 (PD-1) immune checkpoint...

Application of the Immunoscore as prognostic tool for hepatocellular carcinoma

To date, the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) tumor, nodes, metastasis (TNM) classification represents the standard system for evaluation of prognosis in solid tumors. However, the clinical outcome can be significantly different in patients with the same TNM stage. Therefore, many efforts have been made aiming to...

Metastatic Merkel cell carcinoma response to nivolumab

Background Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with limited treatment options. Several lines of evidence support the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis as a likely contributor to immune evasion in MCC. Case presentation We report a case of a patient with metastatic MCC with a significant and durable response...

PD1/PD-L1 inhibition as a potential radiosensitizer in head and neck squamous cell carcinoma: a case report

Background Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint...