Mucorales-Specific T Cells in Patients with Hematologic Malignancies

PLoS One. 2016 Feb 12;11(2):e0149108. doi: 10.1371/journal.pone.0149108. eCollection 2016.

Abstract

Background: Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients.

Methods and findings: By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD.

Conclusions: Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Humans
  • Immunocompromised Host*
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / microbiology
  • Male
  • Middle Aged
  • Mucorales / immunology*
  • Mucormycosis / diagnostic imaging
  • Mucormycosis / immunology*
  • Mucormycosis / microbiology
  • Radiography
  • Th2 Cells / immunology*
  • Th2 Cells / microbiology
  • Young Adult

Grants and funding

This work was supported by the Associazione Italiana per la Ricerca sul Cancro [grant number AIRC IG-14797], Milan, Italy (ML); the Associazione Italiana Lotta alle Leucemie, Linfoma e Mieloma (AIL)-Sezione ‘‘Luciano Pavarotti’’-Modena-ONLUS (LP and FF); Gilead Fellowship Program 2012–2014 (ML); the Societa` Italiana di Ematologia Sperimentale (SIES, ‘‘Piero Martino’’ awarded to LP); and research funds by Gilead Sciences to ML. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.