Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment

Lombardi, Giuseppe; Rumiato, Enrica; Bertorelle, Roberta; Saggioro, Daniela; Farina, Patrizia; Puppa, Alessandro Della; Zustovich, Fable; Berti, Franco; Sacchetto, Valeria; Marcato, Raffaella; Amadori, Alberto; Zagonel, Vittorina

doi:10.1097/coc.0b013e3182a790ea

Cited by 56 publications

(35 citation statements)

References 25 publications

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“…Current standard of care includes surgery, systemic temozolomide (TMZ), and radiation. Systemic chemotherapy (SC) is thought to damage the bone marrow (BM) and subsequently affect the number and activation state of resident immune cells (4), raising concerns for potential antagonistic interactions between SC and immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Anti–PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM

et al. 2016

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The immunosuppressive effects of chemotherapy present a challenge for designing effective cancer immunotherapy strategies. We hypothesized that although systemic chemotherapy (SC) exhibits negative immunologic effects, local chemotherapy (LC) can potentiate an antitumor immune response. We show that LC combined with anti–programmed cell death protein 1 (PD-1) facilitates an antitumor immune response and improves survival (P < 0.001) in glioblastoma. LC-treated mice had increased infiltration of tumor-associated dendritic cells and clonal expansion of antigen-specific T effector cells. In comparison, SC resulted in systemic and intratumoral lymphodepletion, with decreased immune memory in long-term survivors. Furthermore, adoptive transfer of CD8+ cells from LC-treated mice partially rescued SC-treated mice after tumor rechallenge. Last, the timing of chemo- and immunotherapy had differential effects on anti–PD-1 efficacy. This study suggests that both mode of delivery and timing have distinct effects on the efficacy of anti–PD-1. The results of this work could help guide the selection and scheduling of combination treatment for patients with glioblastoma and other tumor types.

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Section: Introductionmentioning

confidence: 99%

Anti–PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM

et al. 2016

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“…9 At this time, we are continuing to be more conservative with dosing in women, particularly with higher BSA and/or lower creatinine clearance. A prospective series of glioblastoma patients receiving full-dose chemo-radiotherapy and adjuvant chemotherapy found that methylated O6-methyl-guanine-DNA methyltransferase promoter and specific pleomorphic variants of the cytochrome P450 oxidoreductase and methionine adenosyltransferase 1A genes in plasma are independent predictors of thrombocytopenia.…”

Section: Discussionmentioning

confidence: 99%

Clinical correlates of severe thrombocytopenia from temozolomide in glioblastoma patients

Arulananda

Liew

Wada

et al. 2018

Internal Medicine Journal

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“…Tumour-associated myeloid cells contribute significantly to the tumour mass, and have been proposed to promote tumour growth, survival, and invasion of surrounding tissues by producing growth factors, cytokines, and proteolytic enzymes [179,183]. Alkylating agents such as temozolomide (TMZ) are the standard therapy for glioblastoma, and commonly result in profound myelosuppression [184]. …”

Section: Myeloid Cells: the White Knights Of Cns Therapy?mentioning

confidence: 99%

Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System

Harrison-Brown

Liu

Bánati

2016

IJMS

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Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as “assistants” in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several ‘checkpoints’ from the blood to their destination in the brain parenchyma. As important components of the neurovascular unit, the functional state changes associated with lineage heterogeneity of myeloid cells are increasingly recognized as important for disease progression. In this review, we discuss some of the cellular elements associated with formation and function of the neurovascular unit, and present an update on the impact of myeloid cells on central nervous system (CNS) diseases in the laboratory and the clinic. We then discuss emerging strategies for harnessing the potential of site-directed myeloid cell homing to the CNS, and identify promising avenues for future research, with particular emphasis on the importance of untangling the functional heterogeneity within existing myeloid subsets.

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Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment

Cited by 56 publications

References 25 publications

Anti–PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM

Anti–PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM

Clinical correlates of severe thrombocytopenia from temozolomide in glioblastoma patients

Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System

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