Immunotherapy approaches for hematological cancers

Lanier, Olivia L.; Pérez-Herrero, Edgar; Andrea, Abielle P. D’; Bahrami, Kiana; Lee, Elaine; Ward, Deidra M.; Ayala-Suárez, Nilaya; Rodríguez-Méndez, Sheyla M.; Peppas, Nicholas A.

doi:10.1016/j.isci.2022.105326

Cited by 13 publications

(12 citation statements)

References 224 publications

(332 reference statements)

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“…There is variability in study methodologies and results, increasing recognition of antibioticrelated adverse events, and concerns about the increasing prevalence of AMR. Additionally, interpretation of fluoroquinolone prophylaxis studies is inherently difficult due to the rapidly evolving cancer landscape; key changes over time that could influence infection-related outcomes include cancer epidemiology, such as increasing age of cancer patients, 99 cancer treatment, such as the increasing use of immunotherapies, 100 and improvements in prevention, diagnosis, and management of infections. 50 These changing variables may reduce study generalizability over time and impact the utility of systematic reviews and meta-analyses.…”

Section: Discussionmentioning

confidence: 99%

Fluoroquinolone prophylaxis in patients with neutropenia at high risk of serious infections: Exploring pros and cons

Singh,

Thursky,

Maron

et al. 2023

Transplant Infectious Dis

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BackgroundThe use of fluoroquinolones to prevent infections in neutropenic patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT) is a controversial issue, with international guidelines providing conflicting recommendations. Although potential benefits are clear, concerns revolve around efficacy, potential harms, and antimicrobial resistance (AMR) implications.DiscussionFluoroquinolone prophylaxis reduces neutropenic fever (NF) bloodstream infections and other serious bacterial infections, based on evidence from systematic reviews, randomized controlled trials, and observational studies in adults and children. Fluoroquinolone prophylaxis may also reduce infection‐related morbidity and healthcare costs; however, evidence is conflicting. Adverse effects of fluoroquinolones are well recognized in the general population; however, studies in the cancer cohort where it is used for a defined period of neutropenia have not reflected this. The largest concern for routine use of fluoroquinolone prophylaxis remains AMR, as many, but not all, observational studies have found that fluoroquinolone prophylaxis might increase the risk of AMR, and some studies have suggested negative impacts on patient outcomes as a result.ConclusionsThe debate surrounding fluoroquinolone prophylaxis calls for individualized risk assessment based on patient characteristics and local AMR patterns, and prophylaxis should be restricted to patients at the highest risk of serious infection during the highest risk periods to ensure that the risk‐benefit analysis is in favor of individual and community benefit. More research is needed to address important unanswered questions about fluoroquinolone prophylaxis in neutropenic patients with cancer or receiving HSCT.

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Section: Discussionmentioning

confidence: 99%

Fluoroquinolone prophylaxis in patients with neutropenia at high risk of serious infections: Exploring pros and cons

Singh,

Thursky,

Maron

et al. 2023

Transplant Infectious Dis

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Section: T-cell Exhaustion and Disease Severitymentioning

confidence: 99%

“…Upon stimulation, T cells may exhibit significant amounts of immunological checkpoints that are suppressive, including PD-1, TIM-3, CTLA-4, and TIGIT ( Figure 3 ) [ 135 , 136 ]. On the other hand, chronic antigen stimulation might cause the development of inhibitory immunological checkpoints, which can cause a condition generally called T-cell exhaustion, which has been reported in severe viral infections [ 136 , 137 , 138 ]. The upregulation of inhibitory immunological checkpoints and the decreased expression of certain genes that produce certain essential cytokines and cytolytic molecules are signs that T cells in patients with severe viral infections or high viral loads may have a disturbed phenotype [ 139 , 140 , 141 , 142 ].…”

Section: T-cell Exhaustion and Disease Severitymentioning

confidence: 99%

“…This suggests functional perturbations in the NK and CD8+ T cells of patients with COVID-19. It is important to consider that some researchers contradict the idea that certain markers, such as PD-1, are not the essential characteristics of exhausted T cells [ 136 , 144 ]. Additional research is necessary to evaluate if immune checkpoint upregulation is caused by T-cell exhaustion or not, even though these results show that it is present in T cells from COVID-19 patients, especially those with severe symptoms [ 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 ].…”

Section: T-cell Exhaustion and Disease Severitymentioning

confidence: 99%

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Updated Insights into the T Cell-Mediated Immune Response against SARS-CoV-2: A Step towards Efficient and Reliable Vaccines

et al. 2023

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The emergence of novel variants of SARS-CoV-2 and their abilities to evade the immune response elicited through presently available vaccination makes it essential to recognize the mechanisms through which SARS-CoV-2 interacts with the human immune response. It is essential not only to comprehend the infection mechanism of SARS-CoV-2 but also for the generation of effective and reliable vaccines against COVID-19. The effectiveness of the vaccine is supported by the adaptive immune response, which mainly consists of B and T cells, which play a critical role in deciding the prognosis of the COVID-19 disease. T cells are essential for reducing the viral load and containing the infection. A plethora of viral proteins can be recognized by T cells and provide a broad range of protection, especially amid the emergence of novel variants of SARS-CoV-2. However, the hyperactivation of the effector T cells and reduced number of lymphocytes have been found to be the key characteristics of the severe disease. Notably, excessive T cell activation may cause acute respiratory distress syndrome (ARDS) by producing unwarranted and excessive amounts of cytokines and chemokines. Nevertheless, it is still unknown how T-cell-mediated immune responses function in determining the prognosis of SARS-CoV-2 infection. Additionally, it is unknown how the functional perturbations in the T cells lead to the severe form of the disease and to reduced protection not only against SARS-CoV-2 but many other viral infections. Hence, an updated review has been developed to understand the involvement of T cells in the infection mechanism, which in turn determines the prognosis of the disease. Importantly, we have also focused on the T cells’ exhaustion under certain conditions and how these functional perturbations can be modulated for an effective immune response against SARS-CoV-2. Additionally, a range of therapeutic strategies has been discussed that can elevate the T cell-mediated immune response either directly or indirectly.

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“…T cell-based cellular immunotherapies such as adoptive cellular therapy and chimeric antigen receptor therapy have shown remarkable clinical success in extending the survival of patients with hematological malignancies 1, 2 . Similar efficacies have not been observed in patients with solid cancer due in part to the highly suppressive nature of the tumor microenvironment (TME) 3 .…”

Section: Introductionmentioning

confidence: 99%

Adaptive IRE1 Signaling Elicits T Cell Metabolic Remodeling and Tumor Control

Riesenberg,

Gandy,

Kennedy

et al. 2023

Preprint

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SummaryThe efficacy of cancer immunotherapies is limited by the metabolic instability of the tumor microenvironment (TME) that disables T cell antitumor immunity. Metabolic imbalances within the TME are sensed and responded to by stress sensors of the endoplasmic reticulum (ER) unfolded protein response (UPR). The UPR comprises three integrated signaling pathways harboring both adaptive and deleterious phases based on the extent and duration of cell stress. Here, we elucidate the differential contributions of adaptive and deleterious signaling downstream of the UPR IRE1 pathway in T cell-regulated tumor control. T cells in murine and patient cancers experience persistent ER stress, leading to hyperactive IRE1 signaling that limits tumor control. However, amplifying the adaptive arm of the IRE1 UPR serves to eliminate mitochondrial toxicity and protect T cells from chronic ER stress, yielding robust tumor engraftment and long-term tumor immunity. Our findings establish the UPR’s essential protective role in antitumor immunity.

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Immunotherapy approaches for hematological cancers

Cited by 13 publications

References 224 publications

Fluoroquinolone prophylaxis in patients with neutropenia at high risk of serious infections: Exploring pros and cons

Fluoroquinolone prophylaxis in patients with neutropenia at high risk of serious infections: Exploring pros and cons

Updated Insights into the T Cell-Mediated Immune Response against SARS-CoV-2: A Step towards Efficient and Reliable Vaccines

Adaptive IRE1 Signaling Elicits T Cell Metabolic Remodeling and Tumor Control

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