Precision medicine in the clinical management of respiratory tract infections including multidrug-resistant tuberculosis: learning from innovations in immuno-oncology

Curr Opin Pulm Med. 2019 May;25(3):233-241. doi: 10.1097/MCP.0000000000000575.

Abstract

Purpose of review: In the light of poor management outcomes of antibiotic-resistant respiratory tract infection (RTI)-associated sepsis syndrome and multidrug-resistant tuberculosis (MDR-TB), new management interventions based on host-directed therapies (HDTs) are warranted to improve morbidity, mortality and long-term functional outcomes. We review developments in potential HDTs based on precision cancer therapy concepts applicable to RTIs including MDR-TB.

Recent findings: Immune reactivity, tissue destruction and repair processes identified during studies of cancer immunotherapy share common pathogenetic mechanisms with RTI-associated sepsis syndrome and MDR-TB. T-cell receptors (TCRs) and chimeric antigen receptors targeting pathogen-specific or host-derived mutated molecules (major histocompatibility class-dependent/ major histocompatibility class-independent) can be engineered for recognition by TCR γδ and natural killer (NK) cells. T-cell subsets and, more recently, NK cells are shown to be host-protective. These cells can also be activated by immune checkpoint inhibitor (ICI) or derived from allogeneic sources and serve as potential for improving clinical outcomes in RTIs and MDR-TB.

Summary: Recent developments of immunotherapy in cancer reveal common pathways in immune reactivity, tissue destruction and repair. RTIs-related sepsis syndrome exhibits mixed immune reactions, making cytokine or ICI therapy guided by robust biomarker analyses, viable treatment options.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antitubercular Agents / therapeutic use
  • Cytokines
  • Humans
  • Immunotherapy*
  • Killer Cells, Natural / immunology
  • Neoplasms / therapy
  • Precision Medicine*
  • Respiratory Tract Infections / drug therapy
  • Respiratory Tract Infections / immunology
  • Respiratory Tract Infections / therapy*
  • T-Lymphocyte Subsets / immunology
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / immunology
  • Tuberculosis, Multidrug-Resistant / therapy*

Substances

  • Antitubercular Agents
  • Cytokines