Cytomegalovirus induces apoptosis in acute leukemia cells as a virus-versus-leukemia function

Koldehoff, Michael; Lindemann, Monika; Opalka, Bertram; Bauer, Sebastian; Ross, Rudolf Stefan; Elmaagacli, Ahmet H.

doi:10.3109/10428194.2015.1032968

Cited by 22 publications

(18 citation statements)

References 34 publications

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“…CMV protein has been found in multiple human tumors [28–31], can infect leukemia and melanoma in vitro [24, 32, 33] and we have seen MCMV DNA in B16F0 tumors from acutely and latently infected animals (data not shown). Thus, it is possible that MCMV-specific T cells entered tumors because the tumors were infected.…”

Section: Resultsmentioning

confidence: 60%

Virus-Specific CD8+ T Cells Infiltrate Melanoma Lesions and Retain Function Independently of PD-1 Expression

Erkes

Smith

Wilski

et al. 2017

The Journal of Immunology

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It is well known that CD8+ tumor infiltrating lymphocytes (TIL) are correlated with positive prognoses in cancer patients and used to determine efficacy of immune therapies. While it is generally assumed that CD8+ TIL will be tumor associated antigen (TAA)-specific, it is unknown whether CD8+ T cells with specificity for common pathogens also infiltrate tumors. If so, the presence of these T cells could alter the interpretation of prognostic and diagnostic TIL assays. We compared TAA-specific and virus-specific CD8+ T cells in the same tumors using murine cytomegalovirus (MCMV), a herpesvirus that causes a persistent/latent infection, and Vaccinia virus (VacV), a poxvirus that is cleared by the host. Virus-specific CD8+ TIL migrated into cutaneous melanoma lesions during acute infection with either virus, as well as after a cleared VacV infection, and during a persistent/latent MCMV infection. Virus-specific TILs developed independent of viral antigen in the tumor and interestingly, expressed low or intermediate levels of full-length PD-1 in the tumor environment. Importantly, PD-1 expression could be markedly induced by antigen, but did not correlate with dysfunction for virus-specific TIL, in sharp contrast to TAA-specific TIL in the same tumors. These data suggest that CD8+ TIL can reflect an individual's immune status, rather than exclusively representing TAA-specific T cells, and that PD-1 expression on CD8+ TIL is not always associated with repeated antigen encounter or dysfunction. Thus, functional virus-specific CD8+ TIL could skew the results of prognostic or diagnostic TIL assays.

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Section: Resultsmentioning

confidence: 60%

Virus-Specific CD8+ T Cells Infiltrate Melanoma Lesions and Retain Function Independently of PD-1 Expression

Erkes

Smith

Wilski

et al. 2017

The Journal of Immunology

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“…[17] Moreover, a direct CMV's cytotoxic effect had recently been shown against blast cells, inducing apoptosis. [18] However, viral reactivations are still associated with an increased risk of NRM and thus, choosing a donor according to CMV serostatus has now become a dilemma. Larger prospective studies in well-defined AML populations with respect to disease status, minimal residual disease, conditioning regimen, GVHD prophylaxis, and antiviral therapy are needed to clearly determine the clinical application of these finding.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of viral reactivations in acute myeloid leukemia patients undergoing allogeneic stem cell transplantation in first complete response

et al. 2016

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Cytomegalovirus (CMV) serological status of donor and recipient as well as CMV reactivation have been associated with a lower risk of relapse in acute myeloid leukemia (AML) patients after allogeneic stem cell transplantation (alloSCT). Since immunosuppression following transplant allows resurgence of many other viruses, we retrospectively evaluated the impact of viral reactivations on relapse and survival in a cohort of 136 AML patients undergoing alloSCT in first remission from sibling (68%) or unrelated (32%) donors. Myeloablative and reduced-intensity conditioning regimen were given to 71 and 65 patients, respectively. Including CMV reactivations, at least 1 viral reactivation was recorded in 76 patients. Viral reactivations were associated with a lower risk of relapse (adjusted HR 0.14; 95% CI 0.07–0.30; P < 0.01), better disease-free survival (aHR 0.29; 95% CI 0.16–0.54; P < 0.01) but higher non relapse mortality. This translated into a better overall survival (aHR 0.44; 95%CI 0.25–0.77; P < 0.01) in patients who experienced viral reactivation. Thus, viral reactivations, including but not limited to CMV reactivation, are associated with a better outcome particularly with regard to the risk of relapse in AML patients undergoing alloSCT. New guidelines regarding the choice of donor according to the CMV serostatus are needed.

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“…13 Nevertheless, CMV also has direct cytotoxic effects in infected blasts, inducing apoptosis as shown recently. 18 Figure 1 shows different CMV-induced antileukemic effects.…”

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confidence: 99%

Cytomegalovirus replication reduces the relapse incidence in patients with acute myeloid leukemia

Elmaagacli¹,

Koldehoff

2016

Blood

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Cytomegalovirus induces apoptosis in acute leukemia cells as a virus-versus-leukemia function

Cited by 22 publications

References 34 publications

Virus-Specific CD8+ T Cells Infiltrate Melanoma Lesions and Retain Function Independently of PD-1 Expression

Virus-Specific CD8+ T Cells Infiltrate Melanoma Lesions and Retain Function Independently of PD-1 Expression

Prognostic impact of viral reactivations in acute myeloid leukemia patients undergoing allogeneic stem cell transplantation in first complete response

Cytomegalovirus replication reduces the relapse incidence in patients with acute myeloid leukemia

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