Epigenetic Control of Protects Tumor-Infiltrating Lymphocytes from Metabolic Exhaustion.

T-cell exhaustion in cancer is linked to poor clinical outcomes, where evidence suggests T-cell metabolic changes precede functional exhaustion. Direct competition between tumor-infiltrating lymphocytes (TIL) and cancer cells for metabolic resources often renders T cells dysfunctional. Environmental stress produces epigenome remodeling events within TIL resulting from loss of the histone methyltransferase EZH2.

Loss of E-Cadherin Inhibits CD103 Antitumor Activity and Reduces Checkpoint Blockade Responsiveness in Melanoma.

Identifying controlling features of responsiveness to checkpoint blockade therapies is an urgent goal in oncology research. Our group and others have previously shown melanoma tumors resistant to checkpoint blockade display features of mesenchymal transition, including E-cadherin loss. Here, we present the first evidence that E-cadherin from tumor cells facilitate immune attack, using a B16F10 melanoma mouse model in which E-cadherin is exogenously expressed (B16.

Do checkpoint inhibitors rely on gut microbiota to fight cancer?

The field of gut microbiota is of growing interest, especially in the recent discoveries of its interaction with host immune responses, which when disrupted, can further alter immunity. It also plays a role in cancer development, its microenvironment and response to anticancer therapeutics. Several recently published experimental studies had explored the efficacy of modifying microbiota to enhance the response of checkpoint inhibitors, suggesting its beneficial function in cancer management and potential to be targeted as a therapeutic agent to enhance efficacy of checkpoint inhibitors.

Immune surveillance in melanoma: From immune attack to melanoma escape and even counterattack.

Pharmacologic inhibition of the cytotoxic T lymphocyte antigen 4 (CTLA4) and the programmed death receptor-1 (PD1) has resulted in unprecedented durable responses in metastatic melanoma. However, resistance to immunotherapy remains a major challenge. Effective immune surveillance against melanoma requires 4 essential steps: activation of the T lymphocytes, homing of the activated T lymphocytes to the melanoma microenvironment, identification and episode of melanoma cells by activated T lymphocytes, and the sensitivity of melanoma cells to apoptosis.

Indicators of responsiveness to immune checkpoint inhibitors.

Modulation of the immune system can produce anti-tumor responses in various cancer types, including melanoma. Recently, immune checkpoint inhibitors (ICI), in single agent and combination regimens, have produced durable and long-lasting clinical responses in a subset of metastatic melanoma patients. These monoclonal antibodies, developed against CTLA-4 and PD-1, block immune-inhibitory receptors on activated T-cells, amplifying the immune response.

Proteomics and melanoma: a current perspective.

Proteomics is the study of the protein complement of the genome, and this powerful technique complements genomic studies. Proteomic experiments result in the generation of large volumes of data requiring complicated analysis algorithms and subsequent confirmatory studies. Until recently, technological limitations of experimental protocols precluded the use of formalin-fixed tissues for these types of studies.

Role of EZH2 histone methyltrasferase in melanoma progression and metastasis.

There is accumulating evidence that the histone methyltransferase enhancer of zeste homolog 2 (EZH2), the main component of the polycomb-repressive complex 2 (PRC2), is involved in melanoma progression and metastasis. Novel drugs that target and reverse such epigenetic changes may find a way into the management of patients with advanced melanoma. We provide a comprehensive up-to-date review of the role and biology of EZH2 on gene transcription, senescence/apoptosis, melanoma microenvironment, melanocyte stem cells, the immune system, and micro RNA.

Microscopes and Mass Spectrometers.

Proteomics is a relatively young discipline while pathology is one of the oldest forms of scientific inquiry. These two fields have different methods and aims, but have many areas of overlap and shared interests. Cultivation of synergistic projects between physicians who study static images of disease and biologists who study the dynamic environment that produces disease states will help further biomedical research providing new diagnostic, prognostic, and therapeutic approaches.

Quantitative Histone Mass Spectrometry Identifies Elevated Histone H3 Lysine 27 (Lys27) Trimethylation in Melanoma.

Normal cell growth is characterized by a regulated epigenetic program that drives cellular activities such as gene transcription, DNA replication, and DNA damage repair. Perturbation of this epigenetic program can lead to events such as mis-regulation of gene transcription and diseases such as cancer. To begin to understand the epigenetic program correlated to the development of melanoma, we performed a novel quantitative mass spectrometric analysis of histone post-translational modifications mis-regulated in melanoma cell culture as well as patient tumors.

Validity and reliability of the Patient-Reported Arthralgia Inventory: validation of a newly-developed survey instrument to measure arthralgia.

Background: There is a need for a survey instrument to measure arthralgia (joint pain) that has been psychometrically validated in the context of existing reference instruments. We developed the 16-item Patient-Reported Arthralgia Inventory (PRAI) to measure arthralgia severity in 16 joints, in the context of a longitudinal cohort study to assess aromatase inhibitor-associated arthralgia in breast cancer survivors and arthralgia in postmenopausal women without breast cancer. We sought to evaluate the reliability and validity of the PRAI instrument in these populations, as well as to examine the relationship of patient-reported morning stiffness and arthralgia.