Prognostic significance of early lymphocyte recovery in pediatric osteosarcoma

Moore, Colin; Eslin, Don; Levy, A.R.; Roberson, Jessica R.; Giusti, Vincent; Sutphin, Robert M.

doi:10.1002/pbc.22673

Cited by 53 publications

(44 citation statements)

References 41 publications

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“…In patients with OS, a lower number of circulating NK cells was observed in peripheral blood compared to normal controls suggesting that NK cells play a preventive role in OS tumor development [23]. Furthermore, patients undergoing treatment for OS demonstrate better survival outcome with faster absolute lymphocyte recovery compared to patient with slow lymphocyte recovery denoting the antitumor role of the immune system in treatment response [24]. Finally, patients with OS treated with IL-2 in addition to polychemotherapy and surgery showed augmentation in the number and activity of NK cells, the magnitude of which correlated with an improved clinical outcome [25].…”

Section: Discussionmentioning

confidence: 94%

Activated and expanded natural killer cells target osteosarcoma tumor initiating cells in an NKG2D–NKG2DL dependent manner

et al. 2015

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Section: Discussionmentioning

confidence: 94%

Activated and expanded natural killer cells target osteosarcoma tumor initiating cells in an NKG2D–NKG2DL dependent manner

et al. 2015

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“…16,17 More generally, T cell lymphopenia has been shown to be a grave prognostic indicator in multiple types of cancers. [18][19][20][21][22][23] Recently, digital PCR platforms have been developed that offer advantages over real time qPCR including the capability to obtain absolute quantification without external references and to be highly robust to variations in PCR efficiency, thus improving assay precision. [25][26][27] Digital PCR is based on limiting dilution of a sample into a large number of separate PCR reactions.…”

Section: Introductionmentioning

confidence: 99%

A comparison of DNA methylation specific droplet digital PCR (ddPCR) and real time qPCR with flow cytometry in characterizing human T cells in peripheral blood

et al. 2014

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Quantitating the copy number of demethylated CpG promoter sites of the CD3Z gene can be used to estimate the numbers and proportions of T cells in human blood and tissue. Quantitative methylation specific PCR (qPCR) is useful for studying T cells but requires extensive calibration and is imprecise at low copy numbers. Here we compared the performance of a new digital PCR platform (droplet digital PCR or ddPCR) to qPCR using bisulfite converted DNA from 157 blood specimens obtained from ambulatory care controls and patients with primary glioma. We compared both ddPCR and qPCR with conventional flow cytometry (FACS) evaluation of CD3 positive T cells. Repeated measures on the same blood sample revealed ddPCR to be less variable than qPCR. Both qPCR and ddPCR correlated significantly with FACS evaluation of peripheral blood CD3 counts and CD3/total leukocyte values. However, statistical measures of agreement showed that linear concordance was stronger for ddPCR than for qPCR and the absolute values were closer to FACS for ddPCR. Both qPCR and ddPCR could distinguish clinically significant differences in T cell proportions and performed similarly to FACS. Given the higher precision, greater accuracy, and technical simplicity of ddPCR, this approach appears to be a superior DNA methylation based method than conventional qPCR for the assessment of T cells.

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“…Further animal experiments have confirmed that injecting specific T cells into osteosarcoma animal models can prevent disease recurrence and metastasis (Merchant et al, 2007). A series of in vitro and in vivo experiments have found that cytokines produced by T cells are also involved in disease progression, and can intervene the animal model under certain conditions (Loeb, 2009;Moore et al, 2010;Li et al, 2011;Segaliny et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Expression of B7-H3 in cancer tissue during osteosarcoma progression in nude mice

2015

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ABSTRACT. Immune cells might participate in the ontogenesis of osteosarcoma. B7-H3 is a new discovered T cell co-stimulatory molecule that was found to be overexpressed in malignant tumors. We aimed to investigate the dynamic expression level of B7-H3 in nude mice with osteosarcoma. A nude mouse osteosarcoma model was successfully established. B7-H3 expression and distribution changes in the early, middle, and late phases of osteosarcoma formation after tumor implantation were observed. Reverse transcription-polymerase chain reaction and western blot analyses were applied to measure the B7-H3 mRNA and protein dynamic changes. Confocal microscopy and immunohistochemistry were used to determine B7-H3 localization and CD3+ T cell expression, respectively, in osteosarcoma tissue. B7-H3 mRNA and protein levels fluctuated during the process of osteosarcoma formation in the nude mouse model. Expression levels were lower in the early and middle phases, while B7-H3 mRNA and protein were overexpressed in the late stage. Accordingly, CD3+ T cell numbers in the early, middle, and late phases in osteosarcoma tissue were 93 ± 13, 92 ± 12, and 46 ± 15, respectively; they can be seen to have decreased significantly in the late stage (P < 0.05). Overall, our results indicated that the B7-H3 expression level is correlated with tumor volume and severity; therefore, it might serve as a tumor biomarker for osteosarcoma.

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Prognostic significance of early lymphocyte recovery in pediatric osteosarcoma

Abstract: These data demonstrate that early lymphocyte recovery represents a significant prognostic indicator for osteosarcoma. Early identification and risk stratification therapy based on the ALC-14 threshold may improve outcomes and our knowledge of this disease.

Cited by 53 publications

References 41 publications

Activated and expanded natural killer cells target osteosarcoma tumor initiating cells in an NKG2D–NKG2DL dependent manner

Activated and expanded natural killer cells target osteosarcoma tumor initiating cells in an NKG2D–NKG2DL dependent manner

A comparison of DNA methylation specific droplet digital PCR (ddPCR) and real time qPCR with flow cytometry in characterizing human T cells in peripheral blood

Expression of B7-H3 in cancer tissue during osteosarcoma progression in nude mice

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