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Precision medicine in the clinical management of respiratory tract infections including multidrug-resistant tuberculosis

learning from innovations in immuno-oncology

Rao, Martina; Ligeiro, Dariob; Maeurer, Markusa

Current Opinion in Pulmonary Medicine: May 2019 - Volume 25 - Issue 3 - p 233–241
doi: 10.1097/MCP.0000000000000575
INFECTIOUS DISEASES: Edited by Michael S. Niederman and Alimuddin Zumla
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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.

aChampalimaud Centre for the Unknown (CCU), ImmunoSurgery Unit

bLisbon Centre for Blood and Transplantation (Instituto Português do Sangue e Transplantação, IPST), Lisbon, Portugal

Correspondence to Professor Markus Maeurer, Champalimaud Centre for the Unknown, Avenida Brasília, 1400-1438 Lisbon, Portugal. Tel: +351 2120480200; e-mail: markus.maeurer@fundacaochampalimaud.pt

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