Dataset Information

Restoration of Peripheral Intermediate and Classical Monocytes Expressing HLA-DR in Patients With Lung Adenocarcinoma After Platinum-Based Chemotherapy.

ABSTRACT: Lung adenocarcinoma represents one of the lung cancer subtypes with major prevalence. Accumulating evidence indicates that the immune system plays an important role in the evolution of the neoplastic process; additionally, several reports suggest that chemotherapy has an immunomodulatory effect. In order to identify the peripheral subpopulations of leukocytes that may change after chemotherapy, we evaluated several peripheral immune subpopulations of monocytes and lymphocytes by multicolor flow cytometry. In addition, we also measured cytokines and growth factors on plasma in order to evaluate the pro-inflammatory context in patients with lung adenocarcinoma after chemotherapy. We found that HLA-DR+ classical and intermediate monocytes were decreased in patients before chemotherapy, compared to controls. After chemotherapy, the relative percentage of those subpopulations was restored. In addition, interleukin 1?, interleukin 12, and interleukin 5 were increased after chemotherapy compared to prechemotherapy levels, while MIP-1? was decreased.

SUBMITTER: Rivas-Fuentes S

PROVIDER: S-EPMC5900825 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Publications

Restoration of Peripheral Intermediate and Classical Monocytes Expressing HLA-DR in Patients With Lung Adenocarcinoma After Platinum-Based Chemotherapy.

Rivas-Fuentes Selma S Iglesias Anjarath Higuera AH Trejo Ana García AG Castro Daniel Yair Chavarría DYC Figueroa Norma Inclán NI Pérez Teresa Aguirre TA Saldaña Renata Báez RB Rosete Patricia Gorocica PG

Technology in cancer research & treatment 20180101

Lung adenocarcinoma represents one of the lung cancer subtypes with major prevalence. Accumulating evidence indicates that the immune system plays an important role in the evolution of the neoplastic process; additionally, several reports suggest that chemotherapy has an immunomodulatory effect. In order to identify the peripheral subpopulations of leukocytes that may change after chemotherapy, we evaluated several peripheral immune subpopulations of monocytes and lymphocytes by multicolor flow ...[more]

PMID: 29642771

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Project description:Introduction: Malignant pleural mesothelioma (MPM) is a malignancy with a very poor prognosis for which new treatment options are urgently needed. We have previously shown that dendritic cell (DC) immunotherapy provides a clinically feasible treatment option. In the current study, we set out to assess the immunological changes induced by DC immunotherapy in peripheral blood of MPM patients. Methods: Peripheral blood was collected from nine patients enrolled in a phase I dose escalation study, before and after treatment with DCs that were pulsed with an allogeneic tumor lysate preparation consisting of a mixture of five cultured mesothelioma cell lines. We used immune profiling by multiplex flow cytometry to characterize different populations of immune cells. In particular, we determined frequencies of T cell subsets that showed single and combinatorial expression of multiple markers that signify T cell activation, maturation and inhibition. Therapy-induced T cell reactivity was assessed in peptide/MHC multimer stainings using mesothelin as a prototypic target antigen with confirmed expression in the clinical tumor lysate preparation. T cell receptor (TCR) diversity was evaluated by TCRB gene PCR assays. Results: We observed an increase in the numbers of B cells, CD4 and CD8 T cells, but not NK cells at 6 weeks post-treatment. The increases in B and T lymphocytes were not accompanied by major changes in T cell reactivity toward mesothelin nor in TCRB diversity. Notably, we did observe enhanced proportions of CD4 T cells expressing HLA-DR, PD-1 (at 2 weeks after onset of treatment) and ICOS (6 weeks) and a CD8 T cell population expressing LAG3 (2 weeks). Discussion: DC immunotherapy using allogeneic tumor lysate resulted in enhanced frequencies of B cells and T cells in blood. We did not detect a skewed antigen-reactivity of peripheral CD8 T cells. Interestingly, frequencies of CD4 T cells expressing activation markers and PD-1 were increased. These findings indicate a systemic activation of the adaptive immune response and may guide future immune monitoring studies of DC therapies.

Dataset Information

Restoration of Peripheral Intermediate and Classical Monocytes Expressing HLA-DR in Patients With Lung Adenocarcinoma After Platinum-Based Chemotherapy.

Publications

Restoration of Peripheral Intermediate and Classical Monocytes Expressing HLA-DR in Patients With Lung Adenocarcinoma After Platinum-Based Chemotherapy.

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