Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (5 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2019)
    Cover page: Anti–CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers—Response
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2019)

    Purpose

    CTLA-4 was the first inhibitory immune checkpoint to be identified. Two mAbs, ipilimumab (IgG1) and tremelimumab (IgG2), which block the function of CTLA-4, have demonstrated durable clinical activity in a subset of patients with advanced solid malignancies by augmenting effector T-cell-mediated immune responses. Studies in mice suggest that anti-CTLA-4 mAbs may also selectively deplete intratumoral FOXP3+ regulatory T cells via an Fc-dependent mechanism. However, it is unclear whether the depletion of FOXP3+ cells occurs in patients with cancer treated with anti-CTLA-4 therapies.

    Experimental design

    Quantitative IHC was used to evaluate the densities of intratumoral CD4+, CD8+, and FOXP3+ cells in stage-matched melanoma (n = 19), prostate cancer (n = 17), and bladder cancer (n = 9) samples treated with ipilimumab and in paired melanoma tumors (n = 18) treated with tremelimumab. These findings were corroborated with multiparametric mass cytometry analysis of tumor-infiltrating cells from paired fresh melanoma tumors (n = 5) treated with ipilimumab.

    Results

    Both ipilimumab and tremelimumab increase infiltration of intratumoral CD4+ and CD8+ cells without significantly changing or depleting FOXP3+ cells within the tumor microenvironment.

    Conclusions

    Anti-CTLA-4 immunotherapy does not deplete FOXP3+ cells in human tumors, which suggests that their efficacy could be enhanced by modifying the Fc portions of the mAbs to enhance Fc-mediated depletion of intratumoral regulatory T cells.See related commentary by Quezada and Peggs, p. 1130.
      Cover page: Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2018)
      This article summarizes the presentations and recommendations of the tenth annual American Geriatrics Society and National Institute on Aging Bench-to-Bedside research conference, "Sensory Impairment and Cognitive Decline," on October 2-3, 2017, in Bethesda, Maryland. The risk of impairment in hearing, vision, and other senses increases with age, and almost 15% of individuals aged 70 and older have dementia. As the number of older adults increases, sensory and cognitive impairments will affect a growing proportion of the population. To limit its scope, this conference focused on sensory impairments affecting vision and hearing. Comorbid vision, hearing, and cognitive impairments in older adults are more common than would be expected by chance alone, suggesting that some common mechanisms might affect these neurological systems. This workshop explored the mechanisms and consequences of comorbid vision, hearing, and cognitive impairment in older adults; effects of sensory loss on the aging brain; and bench-to-bedside innovations and research opportunities. Presenters and participants identified many research gaps and questions; the top priorities fell into 3 themes: mechanisms, measurement, and interventions. The workshop delineated specific research questions that provide opportunities to improve outcomes in this growing population. J Am Geriatr Soc 66:2052-2058, 2018.
        Cover page: American Geriatrics Society and National Institute on Aging Bench‐to‐Bedside Conference: Sensory Impairment and Cognitive Decline in Older Adults
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2021)

        Background

        The coronavirus disease 2019 (COVID-19) pandemic caused a halt to in-person ambulatory care. We evaluated how the reduction in access to care affected HbA1c testing and patient HbA1c levels.

        Methods

        HbA1c data from 11 institutions were extracted to compare testing volume and the percentage of abnormal results between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (Jan-June 2020, period 2). HbA1c results greater than 6.4% were categorized as abnormal.

        Results

        HbA1C testing volumes decreased in March, April and May by 23, 61 and 40% relative to the corresponding months in 2019. The percentage of abnormal results increased in April, May and June (25, 23, 9%). On average, we found that the frequency of abnormal results increased by 0.31% for every 1% decrease in testing volume (p < 0.0005).

        Conclusion

        HbA1c testing volume for outpatients decreased by up to 70% during the early months of the pandemic. The decrease in testing was associated with an increase in abnormal HbA1c results.
          Cover page: The effect of the Covid-19 shutdown on glycemic testing and control
          • Article
          • Peer Reviewed
          ICTS Publications (2011)

          Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.

            Cover page: Harnessing neuroplasticity for clinical applications.
            Top