The following is a summary of “Paradox of immune checkpoint inhibition re-activating tuberculosis” published in the November 2022 issue of Respiratory by Ahmed, et al.
Immune checkpoints (ICs) limit effective anti-tumor responses by dampening T-cell activation, and IC inhibition (ICI) has emerged as a promising potential treatment for many types of cancer. Protection against tuberculosis (TB) in humans relies only on a response from T cells. Reactivation of latent tuberculosis (TB) can occur when T-cell immunity is boosted in cancer patients by inhibiting the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis.
This result contradicts the common belief that raising T-cell immunity to Mycobacterium tuberculosis will lead to better immunological control of this disease. Evidence from multiple mouse research corroborates the anecdotal human findings that PD-1 deficiency causes severe TB illness and premature death. In light of these findings, our understanding of TB immunity and the role of ICs in this phenomenon has to be re-evaluated. By modulating T-cell responses, ICs play a crucial role in protecting tissues from suffering excessive damage and keeping various effector functions operational.
This hypothesis is supported by data showing that inhibitory receptors control immunopathology in the context of respiratory diseases like influenza. By examining the mechanisms of ICs in general and their function in TB. Finally, researchers discuss the developing paradigm and potential future research directions.