Setdb1-loss induces type-I interferons and immune clearance of melanoma.

Despite recent advances in the treatment of melanoma, many patients with metastatic disease still succumb to their disease. To identify tumor-intrinsic modulators of immunity to melanoma, we performed a whole-genome CRISPR screen in melanoma and identified Setdb1 as well as all components of the HUSH complex. We found that loss of Setdb1 leads to increased immunogenicity and complete tumor clearance in a CD8+ T-cell dependent manner.

New insights into programmed cell death protein 1 blockade-associated cutaneous immune-related adverse events.

Cutaneous side-effects associated with immune checkpoint blockade occur in more than half of patients treated with CTLA-4 and PD-1 inhibitors, and are frequently encountered by dermatologists. The molecular mechanism of cutaneous side-effects is incompletely understood but holds important clues about immune tolerance and the antitumor immune response in the skin. A new landmark study published in suggests a critical functional role for the checkpoint receptor PD-1 in restraining self-reactive T cells, which could help explain how some checkpoint-associated cutaneous side-effects arise.

IL-7R licenses a population of epigenetically poised memory CD8 T cells with superior antitumor efficacy that are critical for melanoma memory.

Recurrence of advanced melanoma after therapy is a major risk factor for reduced survival, and treatment options are limited. Antitumor immune memory plays a critical role in preventing melanoma recurrence and memory T cells could be a potent cell-based therapy, but the identity, and functional properties of the required immune cells are incompletely understood. Here, we show that an IL-7R tumor-specific CD8 population is critical for antitumor memory and can be epigenetically augmented to drive powerful antitumor immune responses.

-loss induces type-I interferons and immune clearance of melanoma.

Despite recent advances in the treatment of melanoma, many patients with metastatic disease still succumb to their disease. To identify tumor-intrinsic modulators of immunity to melanoma, we performed a whole-genome CRISPR screen in melanoma and identified multiple components of the HUSH complex, including , as hits. We found that loss of leads to increased immunogenicity and complete tumor clearance in a CD8+ T-cell dependent manner.

Systemic Tolerance Mediated by Melanoma Brain Tumors Is Reversible by Radiotherapy and Vaccination.

Purpose: Immune responses to antigens originating in the central nervous system (CNS) are generally attenuated, as collateral damage can have devastating consequences. The significance of this finding for the efficacy of tumor-targeted immunotherapies is largely unknown.

Experimental Design: The B16 murine melanoma model was used to compare cytotoxic responses against established tumors in the CNS and in the periphery.

Sleep deprivation impairs cAMP signalling in the hippocampus.

Millions of people regularly obtain insufficient sleep. Given the effect of sleep deprivation on our lives, understanding the cellular and molecular pathways affected by sleep deprivation is clearly of social and clinical importance. One of the major effects of sleep deprivation on the brain is to produce memory deficits in learning models that are dependent on the hippocampus.

A phase II study of perifosine in androgen independent prostate cancer.

Objectives: Perifosine is an alkylphospholipid that has exhibited broad antineoplastic activity in preclinical studies. The primary objective of this study was to determine the clinical efficacy of this agent in the treatment of androgen-independent prostate cancer (AIPC) using PSA and clinical criteria.

Patients And Methods: Nineteen patients with progressive, metastatic AIPC were treated with oral perifosine.