Clinical Implications of Cancer Related Inflammation and Depression: A Critical Review

Background:Neuropsychiatric symptoms are problematic in cancer settings. In addition to poor quality of life, depression is associated with worsened survival. Patients who develop depression that responds to treatment have the same cancer-related survival as those patients who never had depression. Although depression in patients with cancer is common, it is often unrecognized, untreated, or at best, undertreated. There remains untapped potential for underlying cancer-related biology associated with depression to help clinicians correctly identify depressed cancer patients and orchestrate appropriate treatments to address cancer-related depression. Biologically, inflammation has been most vigorously described in its association with depression in otherwise healthy patients and to a significant extent in patients with medical illness. This association is especially relevant to patients with cancer since so many aspects of cancer induce inflammation. In addition to cancer itself, its treatments (e.g., surgery, radiation, chemotherapy, and systemic therapies) and associated factors (e.g., smoking, obesity, aging) are all associated with increased inflammation that can drive immunological changes in the brain followed by depression. This critical review investigates the relationship between depression and cancer-related inflammation. It investigates several hypotheses that support these relationships in cancer patients. Special attention is given to the data that support certain inflammatory markers specific to both cancer and depression, the neurobiological mechanisms by which inflammation can impact neurotransmitters and neurocircuits in the brain, and the data addressing interventions that reduce inflammation and depression in cancer patients, and future directions.

Modulation of the Host Cell Transcriptome and Epigenome by Fusobacterium nucleatum

Fusobacterium nucleatum is a bacterium normally found in the healthy oral cavity but also has an emerging role in colorectal cancer and other cancer settings. The host-microbe interactions of F. nucleatum and its involvement in tumor initiation, progression, and treatment resistance are not fully understood.

Recent Therapeutic Approaches to Modulate the Hippo Pathway in Oncology and Regenerative Medicine

The Hippo pathway is an evolutionary conserved signaling network that regulates essential processes such as organ size, cell proliferation, migration, stemness and apoptosis. Alterations in this pathway are commonly found in solid tumors and can lead to hyperproliferation, resistance to chemotherapy, compensation for mKRAS and tumor immune evasion. As the terminal effectors of the Hippo pathway, the transcriptional coactivators YAP1/TAZ and the transcription factors TEAD1–4 present exciting opportunities to pharmacologically modulate the Hippo biology in cancer settings, inflammation and regenerative medicine. This review will provide an overview of the progress and current strategies to directly and indirectly target the YAP1/TAZ protein–protein interaction (PPI) with TEAD1–4 across multiple modalities, with focus on recent small molecules able to selectively bind to TEAD, block its autopalmitoylation and inhibit YAP1/TAZ–TEAD-dependent transcription in cancer.

Integrative medicine therapies in pain management

Pain is a common and often debilitating symptom in both oncology and non-cancer settings, with conventional medical treatments often limited by adverse effects. Integrative medicine provides non-conventional therapies in a conventional setting, offering an additional option for the treatment of symptoms, including pain. Clinical research supports modalities such as acupuncture, touch therapies, and mind–body medicine (yoga, meditation, music therapy, hypnosis, etc.) in the treatment of pain, most significantly when provided as an ‘add-on’ to conventional palliative and supportive care. The Society for Integrative Oncology’s evidence-based guidelines on the use of integrative medicine in patients with breast cancer include the treatment of pain and exacerbating factors such as anxiety and stress. These guidelines have been endorsed by the American Society for Clinical Oncology and are in keeping with those recommended by the National Comprehensive Cancer Network. This chapter examines the effectiveness of integrative medicine in the treatment of pain in both oncology and non-cancer settings. An open and effective collaboration is needed among integrative physicians, who understand both paradigms of care, and palliative care professionals. Ways in which this collaboration can be advanced and future directions for research in the treatment of pain in palliative care are discussed.

Religion and Spirituality in Oncology: An Exploratory Study of the Communication Experiences of Clinicians in Poland

Communication with patients regarding oncology-related aspects is a challenging experience and requires a high level of skill from the interlocutors. The aim of this study was to verify the influence of religion/spirituality in oncological settings from the health professionals’ perspectives in Poland. It assessed the role of religion/spirituality in patient-clinician communication, death or stress self-management, empathy, and breaking bad news skills. Data collection was carried out through a standardized self-administered questionnaire with varying scales. The study cohort consisted of 60 medical practitioners specializing in oncological radiotherapy treatments. It was observed that strategies used for coping with patients’ death, stress reduction, empathy, communication with patients and/or their relatives, or breaking bad news skills, may be gender-specific or may depend on the length of time employed, as well as experience in a cancer-related work environment. This study shows that spirituality and religiousness can support clinicians in managing challenging or negative emotions related to their work in cancer settings. Religiousness and spirituality can also serve as a potential therapeutic strategies for those exposed to patient suffering and death.

Histamine receptor 2 blockade selectively impacts B and T cells in healthy subjects

Histamine receptor 2 (H2R) blockade is commonly used in patients with gastric, duodenal ulcers or gastroesophageal reflux disease. Beyond the gastrointestinal tract, H2R is expressed by multiple immune cells, yet little is known about the immunomodulatory effects of such treatment. Clinical reports have associated H2R blockade with leukopenia, neutropenia, and myelosuppression, and has been shown to provide clinical benefit in certain cancer settings. To systematically assess effects of H2R blockade on key immune parameters, a single-center, single-arm clinical study was conducted in 29 healthy subjects. Subjects received daily high dose ranitidine for 6 weeks. Peripheral blood immunophenotyping and mediator analysis were performed at baseline, 3 and 6 weeks into treatment, and 12 weeks after treatment cessation. Ranitidine was well-tolerated, and no drug related adverse events were observed. Ranitidine had no effect on number of neutrophils, basophils or eosinophils. However, ranitidine decreased numbers of B cells and IL-2Rα (CD25) expressing T cells that remained lower even after treatment cessation. Reduced serum levels of IL-2 were also observed and remained low after treatment. These observations highlight a previously unrecognised immunomodulatory sustained impact of H2R blockade. Therefore, the immune impacts of H2R blockade may require greater consideration in the context of vaccination and immunotherapy.

Mast Cells and Skin and Breast Cancers: A Complicated and Microenvironment-Dependent Role

Mast cells are important sentinel cells in host defense against infection and major effector cells in allergic disease. The role of these cells in cancer settings has been widely debated. The diverse range of mast cell functions in both immunity and tissue remodeling events, such as angiogenesis, provides multiple opportunities for mast cells to modify the tumor microenvironment. In this review, we consider both skin and breast cancer settings to address the controversy surrounding the importance of mast cells in the host response to tumors. We specifically address the key mediators produced by mast cells which impact tumor development. The role of environmental challenges in modifying mast cell responses and opportunities to modify mast cell responses to enhance anti-tumor immunity are also considered. While the mast cell’s role in many cancer contexts is complicated and poorly understood, the activities of these tissue resident and radioresistant cells can provide important opportunities to enhance anti-cancer responses and limit cancer development.

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

Persistent liver inflammation can lead to cirrhosis, which associates with significant morbidity and mortality worldwide. There are no curative treatments beyond transplantation, followed by long-term immunosuppression. The global burden of end stage liver disease has been increasing and there is a shortage of donor organs, therefore new therapies are desperately needed. Harnessing the power of the immune system has shown promise in certain autoimmunity and cancer settings. In the context of the liver, regulatory T cell (Treg) therapies are in development. The hypothesis is that these specialized lymphocytes that dampen inflammation may reduce liver injury in patients with chronic, progressive diseases, and promote transplant tolerance. Various strategies including intrinsic and extracorporeal expansion of Treg cells, aim to increase their abundance to suppress immune responses. We recently discovered that hepatocytes engulf and delete Treg cells by enclysis. Herein, we propose that inhibition of enclysis may potentiate existing regulatory T cell therapeutic approaches in patients with autoimmune liver diseases and in patients receiving a transplant. Moreover, in settings where the abundance of Treg cells could hinder beneficial immunity, such us in chronic viral infection or liver cancer, enhancement of enclysis could result in transient, localized reduction of Treg cell numbers and tip the balance towards antiviral and anti-tumor immunity. We describe enclysis as is a natural process of liver immune regulation that lends itself to therapeutic targeting, particularly in combination with current Treg cell approaches.