Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Brain Behav Immun Health ; 42: 100865, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39411424

RESUMO

Multiple myeloma is a haematological cancer characterised by the accumulation of clonal plasma cells in the bone marrow and is commonly treated with daratumumab, an anti-CD38 monoclonal antibody immunotherapy. Daratumumab often fails to induce stringent complete responses, due in part to resistance to antibody-dependent cellular cytotoxicity (ADCC) exerted by natural killer (NK)-cells and monocytes. Exercise bouts undertaken by healthy people induce lymphocytosis in blood, including to NK-cells and B-cells, but the effects of exercise are unknown in myeloma patients. In addition, whether exercise mobilises plasma cells has not been adequately investigated, and as such the potential impact of exercise on daratumumab treatment is unclear. In this exploratory pilot study, n = 16 smouldering multiple myeloma participants enrolled and n = 9 completed the study which comprised a bout of cycling 15% above anaerobic threshold for ∼30-min, with blood samples collected pre-, immediately post-, and 30-min post-exercise. Peripheral blood mononuclear cells were isolated from blood samples and incubated with the RPMI-8226 plasmacytoma cell line, with or without the presence of daratumumab to determine specific lysis using a calcein-release assay. Daratumumab-mediated cell lysis increased from 18.8% to 23.2% pre- to post-exercise, respectively (p < 0.001), owing to an increased frequency of CD3-CD56+CD16+ NK-cells (+348%), HLA-DR+CD14dimCD16+ monocytes (+125%), and HLA-DR+CD14+CD32+ monocytes (+41%) in blood (p < 0.01). However, overall, total plasma cells (CD38+CD138+) nor clonal plasma cells (CD38brightCD138+CD45-/dimCD19- with light-chain restriction) increased in blood (p > 0.05). Notably, we observed a 305% increase in NK-cells expressing CD38, the daratumumab target antigen, which might render NK-cells more susceptible to daratumumab-mediated fratricide - whereby NK-cells initiate ADCC against daratumumab-bound NK-cells. In conclusion, exercise modestly improved the efficacy of daratumumab-mediated ADCC in vitro. However, plasma cells were largely unchanged, and NK-cells expressing CD38 - the daratumumab target antigen - increased in blood. Future research should consider the optimal timings of exercise during daratumumab treatment in myeloma to avert exacerbation of daratumumab-mediated NK-cell lysis.

2.
Brain Behav Immun ; 118: 468-479, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38503395

RESUMO

Chronic lymphocytic leukaemia (CLL) is characterised by the clonal proliferation and accumulation of mature B-cells and is often treated with rituximab, an anti-CD20 monoclonal antibody immunotherapy. Rituximab often fails to induce stringent disease eradication, due in part to failure of antibody-dependent cellular cytotoxicity (ADCC) which relies on natural killer (NK)-cells binding to rituximab-bound CD20 on B-cells. CLL cells are diffusely spread across lymphoid and other bodily tissues, and ADCC resistance in survival niches may be due to several factors including low NK-cell frequency and a suppressive stromal environment that promotes CLL cell survival. It is well established that exercise bouts induce a transient relocation of NK-cells and B-cells into peripheral blood, which could be harnessed to enhance the efficacy of rituximab in CLL by relocating both target and effector cells together with rituximab in blood. In this pilot study, n = 20 patients with treatment-naïve CLL completed a bout of cycling 15 % above anaerobic threshold for âˆ¼ 30-minutes, with blood samples collected pre-, immediately post-, and 1-hour post-exercise. Flow cytometry revealed that exercise evoked a 254 % increase in effector (CD3-CD56+CD16+) NK-cells in blood, and a 67 % increase in CD5+CD19+CD20+ CLL cells in blood (all p < 0.005). NK-cells were isolated from blood samples pre-, and immediately post-exercise and incubated with primary isolated CLL cells with or without the presence of rituximab to determine specific lysis using a calcein-release assay. Rituximab-mediated cell lysis increased by 129 % following exercise (p < 0.001). Direct NK-cell lysis of CLL cells - independent of rituximab - was unchanged following exercise (p = 0.25). We conclude that exercise improved the efficacy of rituximab-mediated ADCC against autologous CLL cells ex vivo and propose that exercise should be explored as a means of enhancing clinical responses in patients receiving anti-CD20 immunotherapy.


Assuntos
Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Humanos , Rituximab/farmacologia , Rituximab/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Projetos Piloto , Anticorpos Monoclonais Murinos/farmacologia , Anticorpos Monoclonais Murinos/uso terapêutico
3.
Front Oncol ; 13: 1244090, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37681023

RESUMO

Therapeutic monoclonal antibodies (mAbs) are standard care for many B-cell haematological cancers. The modes of action for these mAbs include: induction of cancer cell lysis by activating Fcγ-receptors on innate immune cells; opsonising target cells for antibody-dependent cellular cytotoxicity or phagocytosis, and/or triggering the classical complement pathway; the simultaneous binding of cancer cells with T-cells to create an immune synapse and activate perforin-mediated T-cell cytotoxicity against cancer cells; blockade of immune checkpoints to facilitate T-cell cytotoxicity against immunogenic cancer cell clones; and direct delivery of cytotoxic agents via internalisation of mAbs by target cells. While treatment regimens comprising mAb therapy can lead to durable anti-cancer responses, disease relapse is common due to failure of mAb therapy to eradicate minimal residual disease. Factors that limit mAb efficacy include: suboptimal effector cell frequencies, overt immune exhaustion and/or immune anergy, and survival of diffusely spread tumour cells in different stromal niches. In this review, we discuss how immunomodulatory changes arising from exposure to structured bouts of acute exercise might improve mAb treatment efficacy by augmenting (i) antibody-dependent cellular cytotoxicity, (ii) antibody-dependent cellular phagocytosis, (iii) complement-dependent cytotoxicity, (iv) T-cell cytotoxicity, and (v) direct delivery of cytotoxic agents.

4.
BMJ Open ; 12(3): e056132, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35351718

RESUMO

OBJECTIVES: The aim of this study was to explore the experiences of patients with breast, prostate or blood cancer, regarding their (1) engagement with exercise and physical activity during treatment and in the months following standard care, and (2) the meanings attached to these lifestyle behaviours. DESIGN: A qualitative study using focus groups. The groups were audio recorded, transcribed and analysed using Framework analysis. SETTING: A hospital-based cancer treatment centre in the South-West of England. PARTICIPANTS: Eighteen people who had either completed treatment or were currently on maintenance therapy for breast, prostate or blood cancer (non-Hodgkin lymphoma or Hodgkin lymphoma). RESULTS: Participants reported treatment limiting their ability to engage in exercise and physical activity. However, participants were aware of the physiological, emotional and social benefits of exercise and expressed a desire to maintain a physically active lifestyle before, during and after treatment. They noted a lack of concrete guidance and appropriate exercise classes for people with cancer and felt poorly informed about the type, intensity, duration and frequency of exercise they should be undertaking. As such, participants reported making decisions on their own, relying on their intuition and listening to their bodies to gauge whether they were doing enough exercise (or not). CONCLUSIONS: Participants were aware of the benefits of a physically active lifestyle during and following cancer treatment, but were not familiar with exercise and physical activity guidelines for people living with and beyond cancer. There is a need for healthcare professionals, academics and policy makers to determine how exercise and physical activity can be supported in clinical settings in realistic and meaningful ways accommodating individual patient circumstances.


Assuntos
Neoplasias Hematológicas , Neoplasias , Inglaterra , Exercício Físico/psicologia , Grupos Focais , Neoplasias Hematológicas/terapia , Hospitais , Humanos , Masculino , Próstata , Pesquisa Qualitativa
5.
Soc Sci Med ; 264: 113402, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33010714

RESUMO

Improving the patient experience is widely recognised as an important goal in the delivery of high-quality healthcare. This study contributes to this goal with a particular focus on the role of the material hospital environment for patients being treated for cancer. Extending the burgeoning literature utilising materialist theoretical approaches in social science and medicine, we report on qualitative data with 18 participants who had received cancer treatment from one UK hospital. Our analysis offers a typology of ways in which the material hospital environment is affective: through patients' direct intra-actions with nonhuman materiality; through providing shared spaces within which human-human assemblages are actualised; and through being the material component of the practices of treatment. Within each process in this typology, the analysis highlights how the affective feeling states which play a critical role in patient wellbeing are in many ways contingent, fluid and context-sensitive. Amidst ambitions to improve the patient experience, these findings underline the significance of materialities of care and offer a broad explanatory typology with analytic and practical potential for healthcare staff, patient groups, architects and designers.


Assuntos
Hospitais , Neoplasias , Atenção à Saúde , Humanos , Neoplasias/terapia
6.
Physiol Behav ; 194: 191-198, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29763678

RESUMO

Dendritic cells (DCs) are important sentinel cells of the immune system responsible for presenting antigen to T cells. Exercise is known to cause an acute and transient increase in the frequency of DCs in the bloodstream in humans, yet there are contradictory findings in the literature regarding the phenotypic composition of DCs mobilised during exercise, which may have implications for immune regulation and health. Accordingly, we sought to investigate the composition of DC sub-populations mobilised in response to acute aerobic exercise. Nine healthy males (age, 21.9 ±â€¯3.6 years; height, 177.8 ±â€¯5.4 cm; body mass, 78.9 ±â€¯10.8 kg; body mass index, 24.9 ±â€¯3.3 kg·m2; V̇O2 MAX, 41.5 ±â€¯5.1 mL·kg·min-1) cycled for 20 min at 80% V̇O2 MAX. Blood was sampled at baseline, during the final minute of exercise and 30 min later. Using flow cytometry, total DCs were defined as Lineage- (CD3, CD19, CD20, CD14, CD56) HLA-DR+ and subsequently identified as plasmacytoid DCs (CD303+) and myeloid DCs (CD303-). Myeloid DCs were analysed for expression of CD1c and CD141 to yield four sub-populations; CD1c-CD141+; CD1c+CD141+; CD1c+CD141- and CD1c-CD141-. Expression of CD205 was also analysed on all DC sub-populations to identify DCs capable of recognising apoptotic and necrotic cells. Total DCs increased by 150% during exercise (F(1,10) = 60; p < 0.05, η2 = 0.9). Plasmacytoid DCs mobilised to a greater magnitude than myeloid DCs (195 ±â€¯131% vs. 131 ±â€¯100%; p < 0.05). Among myeloid DCs, CD1c-CD141- cells showed the largest exercise-induced mobilisation (167 ±â€¯122%), with a stepwise pattern observed among the remaining sub-populations: CD1c+CD141- (79 ±â€¯50%), followed by CD1c+CD141+ (44 ±â€¯41%), with the smallest response shown by CD1c-CD141+ cells (23 ±â€¯54%) (p < 0.05). Among myeloid DCs, CD205- cells were the most exercise responsive. All DC subsets returned to resting levels within 30 min of exercise cessation. These results show that there is a preferential mobilisation of plasmacytoid DCs during exercise. Given the functional repertoire of plasmacytoid DCs, which includes the production of interferons against viral and bacterial pathogens, these findings indicate that exercise may augment immune-surveillance by preferentially mobilising effector cells; these findings have general implications for the promotion of exercise for health, and specifically for the optimisation of DC harvest for cancer immunotherapy.


Assuntos
Células Dendríticas/fisiologia , Exercício Físico/fisiologia , Antígenos CD/metabolismo , Moléculas de Adesão Celular/metabolismo , Células Dendríticas/citologia , Humanos , Lectinas Tipo C/metabolismo , Masculino , Antígenos de Histocompatibilidade Menor/metabolismo , Receptores de Superfície Celular/metabolismo , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA