Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8+ T cells via ME1 up-regulation.

Patients with advanced cancers who either do not experience initial response to or progress while on immune checkpoint inhibitors (ICIs) receive salvage radiotherapy to reduce tumor burden and tumor-related symptoms. Occasionally, some patients experience substantial global tumor regression with a rebound of cytotoxic CD8+ T cells. We have termed the rebound of cytotoxic CD8+ T cells in response to salvage therapy as T cell resilience and examined the underlying mechanisms of resilience. Resilient T cells are enriched for CX3CR1+ CD8+ T cells with low mitochondrial membrane potential, accumulate less reactive oxygen species (ROS), and express more malic enzyme 1 (ME1). ME1 overexpression enhanced the cytotoxicity and expansion of effector CD8+ T cells partially via the type I interferon pathway. ME1 also increased mitochondrial respiration while maintaining the redox state balance. ME1 increased the cytotoxicity of peripheral lymphocytes from patients with advanced cancers. Thus, preserved resilient T cells in patients rebound after salvage therapy and ME1 enhances their resiliency.

Clinical and cellular phenotypes resulting from a founder mutation in IL10RB.

Inborn errors of immunity are a group of rare genetically determined diseases that impair immune system development or function. Many of these diseases include immune dysregulation, autoimmunity or autoinflammation as prominent clinical features. In some children diagnosed with very early onset inflammatory bowel disease (VEOIBD), monogenic inborn errors of immune dysregulation underlie disease. We report a case of VEOIBD caused by a novel homozygous loss of function mutation in IL10RB. We use CyTOF with a broad panel of antibodies to interrogate the immunophenotype of this patient and detect reduced frequencies of CD4 and CD8 T cells with additional defects in some populations of T helper cells, innate-like T cells and memory B cells. Finally, we identify the patient's mutation as a founder allele in an isolated indigenous population and estimate the age of this variant by studying the shared ancestral haplotype.

Moxibustion for primary dysmenorrhea: A protocol for evidence-based clinical practice guideline.

BACKGROUND: Primary dysmenorrhea (PD) is a common gynecological disease characterized by lower abdominal pain. Moxibustion as a traditional Chinese treatment, can effectively treat PD with few adverse reactions. Nowadays, there is still no standard guideline for moxibustion treatment of PD, so related clinical practice guidelines need to be developed. METHODS: This guideline will be developed in line with the latest guideline definition from Institute of Medicine, and that applies the GRADE system as well as the World Health Organization handbook to appraise the quality of evidence and develop recommendations. We will set up a Guideline working group, put forward the corresponding problems based on the principle of Population, Intervention, Comparison, Outcomes (PICO), and complete the literature retrieval. After achieving consensus through evidence syntheses and 2 to 3 rounds of Delphi process, we will also consider patients values and preferences and implement peer review in the guideline. RESULT: We will put forward evidence-based best practice recommendations and moxibustion standard to improve the symptoms caused by primary dysmenorrhea in a more efficient way. At present, the research is still in progress, and there is no result to report. CONCLUSIONS: This guideline will be helpful to clinical acupuncturists and other professionals to further improve clinical efficacy in treating PD with moxibustion. Moreover, we will also constantly update and evaluate the evidence to both support recommendations and identify gap areas for future research. SYSTEMATIC REVIEW REGISTRATIONS: registration number: IPGRP-2020CN021.