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Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study
ConclusionsThe tolerability of the combined checkpoint blockade in UM may possibly be better than in trials on cutaneous melanoma. This study implies that combined checkpoint blockade represents the hitherto most effective treatment option available for metastatic UM available outside of clinical trials. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 12, 2019 Category: Cancer & Oncology Source Type: research

Domatinostat favors the immunotherapy response by modulating the tumor immune microenvironment (TIME)
ConclusionIn summary, these data suggest a promising potential of domatinostat in combination with immunotherapy to improve the outcome of refractory cancer patients. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 7, 2019 Category: Cancer & Oncology Source Type: research

Secondary resistance to immunotherapy associated with β-catenin pathway activation or PTEN loss in metastatic melanoma
ConclusionOur results suggest that secondary resistance to immunotherapies can arise upon selection for new oncogenic variants that mediate T cell exclusion. To identify the spectrum of underlying mechanisms of therapeutic resistance, similar evaluation for the emergence of tumor-intrinsic alterations in resistant lesions should be done prospectively at the time of relapse in a range of additional patients developing secondary resistance. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 7, 2019 Category: Cancer & Oncology Source Type: research

Guillain-Barre syndrome observed with adoptive transfer of lymphocytes genetically engineered with an NY-ESO-1 reactive T-cell receptor
ConclusionsGiven the expanding applications of immunotherapy in cancer management, clinicians should stay vigilant against the potential development of unusual but life-threatening immune-mediated toxicities. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 7, 2019 Category: Cancer & Oncology Source Type: research

Treatment with checkpoint inhibitors in a metastatic colorectal cancer patient with molecular and immunohistochemical heterogeneity in MSI/dMMR status
ConclusionsThe present case supports the efficacy of immune checkpoint inhibition in mCRC with heterogeneity in MMR/microsatellite instability status. Clinical issues that may arise in these rare patients are discussed in detail. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 7, 2019 Category: Cancer & Oncology Source Type: research

Distinct tumor microenvironments of lytic and blastic bone metastases in prostate cancer patients
AbstractThe most common metastatic lesions of prostate cancer are in bone and can be classified into three distinct pathology subtypes: lytic, blastic, and an indeterminate mixture of both. We investigated a cohort of decalcified formalin-fixed and paraffin-embedded (FFPE) patient specimens from the bone that contained metastatic prostate cancer with lytic or blastic features. These tissue sections were utilized for immunohistochemistry (IHC) staining, isolation of RNA for gene expression, and Digital Spatial Profiling (DSP) of changes in both the tumor and microenvironment. A diverse set of unique immune cell populations ...
Source: Journal for Immunotherapy of Cancer - November 7, 2019 Category: Cancer & Oncology Source Type: research

Targeting of CXCR3 improves anti-myeloma efficacy of adoptively transferred activated natural killer cells
ConclusionsOur results demonstrate that in vitro activation affects NK cell anti-myeloma activity in vivo by regulating their BM infiltration. Furthermore, we provided direct evidence that CXCR3 restrains NK cell anti-tumor capacity in vivo according to the activation protocol used, and that the effects of NK cell-based adoptive immunotherapy for multiple myeloma can be improved by increasing their bone marrow homing through CXCR3 inhibition. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 6, 2019 Category: Cancer & Oncology Source Type: research

Budesonide treatment for microscopic colitis from immune checkpoint inhibitors
ConclusionsGastrointestinal mucosal inflammation without visible mucosal injury is a distinct, prevalent CPI enterocolitis subset that can be diagnosed by endoscopy. First-line budesonide appears effective in controlling “microscopic colitis” symptoms and prolonging immunotherapy duration. These findings present a compelling rationale for routine endoscopic evaluation of suspected CPI enterocolitis and suggest an alternative glucocorticoid-sparing treatment strategy for a subset of such patients. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 6, 2019 Category: Cancer & Oncology Source Type: research

Moving forward to address key unanswered questions on targeting PD-1/PD-L1 in cancer: limitations in preclinical models and the need to incorporate human modifying factors
AbstractThe tremendous clinical success of immune checkpoint inhibition (ICI), particularly targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1/2 (PD-L1/2) pathway, has resulted in application to multiple cancers, as a monotherapy and as a companion to both conventional and novel agents. Despite this, the precise mechanisms underlying the anti-tumor effects of PD-1/PD-L1 blockade remain unclear. Emphasis has centered on its reversal of tumor-specific CD8+ T-cell exhaustion, although many cell types and processes are likely impacted. Due to the complex and pervasive roles of PD-1/PD-L1 on T-cell b...
Source: Journal for Immunotherapy of Cancer - November 6, 2019 Category: Cancer & Oncology Source Type: research

Adoption of immunotherapy in the community for patients diagnosed with metastatic melanoma
ConclusionWhile the use of immunotherapy for metastatic melanoma has increased over time, adoption varies widely across hospitals. Underinsured patients were more likely to receive treatment at low immunotherapy prescribing hospitals. The variation suggests inequity in access to these potentially life-saving drugs. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 6, 2019 Category: Cancer & Oncology Source Type: research

34th Annual Meeting & amp; Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 2
(Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 5, 2019 Category: Cancer & Oncology Source Type: research

Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US Food and Drug Administration adverse events reporting system
ConclusionOur pharmacovigilance analysis shows a high reporting frequency of endocrine AEs provoked by ICI monotherapy (especially anti-CTLA-4 therapy) and further reinforced by combination therapy. In addition, treatment with different ICI immunotherapies may result in a unique and distinct profile of endocrinopathies. Early recognition and management of ICI-related endocrine irAEs is of vital importance in clinical practice. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 5, 2019 Category: Cancer & Oncology Source Type: research

34th Annual Meeting & amp; Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 1
(Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 5, 2019 Category: Cancer & Oncology Source Type: research

Immunostimulatory RNA leads to functional reprogramming of myeloid-derived suppressor cells in pancreatic cancer
ConclusionsWe provide evidence that the treatment with immunostimulatory RNA reprograms the TME of pancreatic cancer by reducing the suppressive activity of MDSC, polarizing myeloid cells into a M1-like state and recruiting DC. We postulate that tumor cell-targeting combination strategies may benefit from RLH-based TME remodeling. In addition, we provide novel insights into the dual role of IFN signaling in MDSC ’s suppressive function and provide evidence that host-intrinsic IFN signaling may be critical for MDSC to gain suppressive function during tumor development. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 5, 2019 Category: Cancer & Oncology Source Type: research

Antibiotic therapy and outcome from immune-checkpoint inhibitors
AbstractSensitivity to immune checkpoint inhibitor (ICPI) therapy is governed by a complex interplay of tumor and host-related determinants. Epidemiological studies have highlighted that exposure to antibiotic therapy influences the probability of response to ICPI and predict for shorter patient survival across malignancies. Whilst a number of studies have reproducibly documented the detrimental effect of broad-spectrum antibiotics, the immune-biologic mechanisms underlying the association with outcome are poorly understood. Perturbation of the gut microbiota, an increasingly well-characterized factor capable of influencin...
Source: Journal for Immunotherapy of Cancer - November 5, 2019 Category: Cancer & Oncology Source Type: research