The immune response to cytomegalovirus in allogeneic hematopoietic stem cell transplant recipients

Ciáurriz, Miriam; Zabalza, Amaya; Beloki, Lorea; Mansilla, Cristina; Pérez-Valderrama, Estela; Lachén, Mercedes; Bandrés, Eva; Olavarría, Eduardo; Ramírez, Natalia

doi:10.1007/s00018-015-1986-z

Cited by 23 publications

(17 citation statements)

References 146 publications

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“…Recovery post-HSCT may also inform consideration of the longer-term immune prospects of breast cancer patients post-chemotherapy with regards to susceptibility to infections. HSCT patients suffer lymphopenia in the months following transplantation and are at high risk of viral reactivations, typically earlier in recovery [ 31 ], and are more prone to bacterial infections later, especially in the case of delayed B cell reconstitution [ 32 , 33 ]. Similarly, viral reactivation is relatively common in breast cancer patients during or shortly after chemotherapy [ 34 , 35 ], although this has not been related to depleted lymphocyte levels.…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer

et al. 2016

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BackgroundApproximately 30 % of breast cancer patients receive chemotherapy, yet little is known about influences of current regimens on circulating lymphocyte levels and phenotypes. Similarly, clinico-pathological factors that modify these influences, and implications for future immune health remain mainly unexplored.MethodsWe used flow-cytometry to assess circulating lymphocyte levels and phenotypes in 88 primary breast cancer patients before chemotherapy and at time-points from 2 weeks to 9 months after chemotherapy completion. We examined circulating titres of antibodies against pneumococcal and tetanus antigens using ELISAs.ResultsLevels of B, T and NK cells were significantly reduced 2 weeks after chemotherapy (p < 0.001). B cells demonstrated particularly dramatic depletion, falling to 5.4 % of pre-chemotherapy levels. Levels of all cells recovered to some extent, although B and CD4+ T cells remained significantly depleted even 9 months post-chemotherapy (p < 0.001). Phenotypes of repopulating B and CD4+ T cells were significantly different from, and showed no sign of returning to pre-chemotherapy profiles. Repopulating B cells were highly depleted in memory cells, with proportions of memory cells falling from 38 % to 10 % (p < 0.001). Conversely, repopulating CD4+ T cells were enriched in memory cells, which increased from 63 % to 75 % (p < 0.001). Differences in chemotherapy regimen and patient smoking were associated with significant differences in depletion extent or repopulation dynamics. Titres of anti-pneumococcal and anti-tetanus antibodies were both significantly reduced post-chemotherapy and did not recover during the study (p < 0.001).ConclusionBreast cancer chemotherapy is associated with long-term changes in immune parameters that should be considered during clinical management.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0669-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer

et al. 2016

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“…CMV remains one of the most problematic pathogens in HCT recipients ( 1 7 ). Since T cell compartments are critical for immune control of CMV, a variety tools have been adopted to measure cell-mediated immunity against CMV for immunological monitoring ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although advances in preemptive treatment based on monitoring viral load determined by pp65 antigenemia assays and/or quantitative PCR for CMV DNA have reduced the incidence of CMV viremia and subsequent disease, breakthrough CMV disease and drug-related toxicity is still a problem ( 3 4 5 ). The T cell system plays a crucial role in controlling CMV infection, and the deficiency of this immune system after HCT creates a risk of CMV replication and shedding ( 6 7 ). Several previous studies have reported that the ELISPOT assay for measuring CMV-specific T cell responses is useful for predicting the development of CMV infection and disease after HCT ( 8 9 10 11 ).…”

Section: Introductionmentioning

confidence: 99%

The Detailed Kinetics of Cytomegalovirus-specific T cell Responses after Hematopoietic Stem Cell Transplantation: 1 Year Follow-up Data

et al. 2018

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The detailed kinetics of the cytomegalovirus (CMV)-specific T cell response in hematopoietic stem cell transplant (HCT) recipients have not yet been fully assessed. We evaluated these kinetics of CMV-specific T cell response and factors associated with high CMV-specific T cell responses 1 year after HCT. In HCT recipients, CMV pp65 and IE1-specific ELISPOT assay were performed before HCT (D0), and at 30 (D30), 90 (D90), 180 (D180), and 360 (D360) days after HCT. Of the 51 HCT recipients with donor-positive (D+)/recipient-positive (R+) serology, 26 (51%) developed CMV infections after HCT. The patterns of post-transplantation reconstitution for CMV-specific T cell response were classified into 4 types: 1) an initial decrease at D30 followed by gradual T cell reconstitution without CMV infection (35%), 2) an initial decrease at D30 followed by gradual T cell reconstitution preceded by CMV infection (35%), 3) failure of gradual or constant T cell reconstitution (26%), and 4) no significant T cell reconstitution (4%). There was no significant difference between ELISPOT counts of D360 and those of D0. High CMV-specific T cell responses at D360 were not associated with high CMV-specific T cell response at D0, CMV infection, ganciclovir therapy, graft versus host disease (GVHD), and immunosuppressant use. In conclusion, there are 4 distinct patterns of reconstitution of the CMV-specific T cell response after HCT. In addition, reconstituted donor-origin CMV-specific T cell responses appeared to be constant until day 360 after HCT, regardless of the level of the pre-transplant CMV-specific T cell response, CMV infection, and immunosuppressant use.

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“…These processes work to slow down viral replication before the adaptive immune response develops adequately. Once the virus disseminates to cells of myeloid lineage, including monocytes and CD34 cells, it establishes a latent infection [57]. CMV-specific CD4 T cells have been described as appearing one week after the peak of CMV replication, and synthesize T helper 1 type (Th1) cytokines including interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α).…”

Section: Cytomegalovirus and Host Immune Responsementioning

confidence: 99%

Cytomegalovirus Infections after Hematopoietic Stem Cell Transplantation: Current Status and Future Immunotherapy

Cho

Lee

Kim

2019

IJMS

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Cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT) is one of the critical infectious complications related to host immune recovery. The spectrum of CMV infection is quite extensive, from asymptomatic CMV reactivation presenting mainly as CMV DNAemia to fatal CMV diseases involving gut, liver, lungs, or brain. In addition to organ involvement, CMV reactivation can exert indirect effects such as immunosuppression or graft failure that may result in the development of concurrent infectious complications. Currently, preemptive therapy, which is based on PCR-based monitoring of CMV from blood, is a mainstay enabling improvement in CMV-related outcomes. During the past decades, new antiviral drugs, clinical trials for prophylaxis in high-risk groups, and vaccines for preventing CMV infection have been introduced. In addition, data for immunologic monitoring and adoptive immunotherapy have also been accumulated. Here, we review the current status and recent updates in this field, with future perspectives including immunotherapy in HSCT recipients.

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The immune response to cytomegalovirus in allogeneic hematopoietic stem cell transplant recipients

Cited by 23 publications

References 146 publications

Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer

Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer

The Detailed Kinetics of Cytomegalovirus-specific T cell Responses after Hematopoietic Stem Cell Transplantation: 1 Year Follow-up Data

Cytomegalovirus Infections after Hematopoietic Stem Cell Transplantation: Current Status and Future Immunotherapy

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