In the Journals

PD-1 blockade may increase risk for, severity of TB infection

A type of cancer immunotherapy may increase the risk for and severity of tuberculosis infection, according to a recent report.

The outcomes of two cancer patients who developed TB after undergoing PD-1 blockade suggest that it may be appropriate to screen such patients for Mycobacterium tuberculosis before treating them with anti-PD-1 drugs, researchers said.

Daniel L. Barber, PhD, chief of the T-Lymphocyte Biology Unit at the National Institute of Allergy and Infectious Diseases, explained the therapy:

“During cancer or persistent infection, T cells can develop defects in their functions needed to control the tumor or pathogen. Part of this loss of T cell function has been shown to be due to the upregulation of inhibitory receptors, often referred to as immune checkpoint molecules, on the dysfunctional T cells,” Barber told Infectious Disease News.

CT image of a chest 
Chest CT images of a patient taken 5 months after the start of PD-1 blockade (left) and 2 months later (right), showing the development of a nodule in the lung (red arrow).
Source: D.L. Barber et al, Science Translational Medicine (2018)

“PD-1 is one such key molecule involved in regulating T cell function in these settings, and boosting T cell function through blockade of the PD-1 pathway has proven to be therapeutically beneficial for several different malignancies. There is also interest in targeting the PD-1 pathway to treat different sorts of infections.”

Barber and colleagues detailed the cases of two cancer patients who contracted TB after PD-1-targeting therapy. According to the report, the first patient developed a fatal case of TB 2 months after receiving nivolumab for throat cancer. The second patient, who received pembrolizumab for skin cancer, was successfully treated for TB.

The researchers characterized the adaptive immune system in the surviving patient and found that “PD-1 blockade was followed by expansion of circulating (M. tuberculosis)-specific TH1 cells, but not (M. tuberculosis)-specific TH17 cells, CD8 T cells or increased antibody responses.”

According to the study, these results were consistent with previous data that suggested that boosting TH1 function with PD-1 blockade may increase the risk or severity of TB in humans and that screening for TB may be warranted.

“When cancer patients are treated with PD-1 blocking agents, it’s not only the immune response to the tumor that’s being impacted,” Barber said. “Although more studies are needed to conclusively show that tuberculosis is a potential adverse event directly resulting from PD-1 blockade, this study clearly indicates we should exercise caution when treating [M. tuberculosis]-infected individuals with this important new class of cancer drugs. It certainly seems warranted to screen for [M. tuberculosis] infection prior to initiating treatment of cancer patients with PD-1- or PD-L1-blocking drugs.”– by Caitlyn Stulpin

Disclosures: Barber reports receiving royalties from patents held relating to PD-1 blockade. All other authors report no relevant financial disclosures.

A type of cancer immunotherapy may increase the risk for and severity of tuberculosis infection, according to a recent report.

The outcomes of two cancer patients who developed TB after undergoing PD-1 blockade suggest that it may be appropriate to screen such patients for Mycobacterium tuberculosis before treating them with anti-PD-1 drugs, researchers said.

Daniel L. Barber, PhD, chief of the T-Lymphocyte Biology Unit at the National Institute of Allergy and Infectious Diseases, explained the therapy:

“During cancer or persistent infection, T cells can develop defects in their functions needed to control the tumor or pathogen. Part of this loss of T cell function has been shown to be due to the upregulation of inhibitory receptors, often referred to as immune checkpoint molecules, on the dysfunctional T cells,” Barber told Infectious Disease News.

CT image of a chest 
Chest CT images of a patient taken 5 months after the start of PD-1 blockade (left) and 2 months later (right), showing the development of a nodule in the lung (red arrow).
Source: D.L. Barber et al, Science Translational Medicine (2018)

“PD-1 is one such key molecule involved in regulating T cell function in these settings, and boosting T cell function through blockade of the PD-1 pathway has proven to be therapeutically beneficial for several different malignancies. There is also interest in targeting the PD-1 pathway to treat different sorts of infections.”

Barber and colleagues detailed the cases of two cancer patients who contracted TB after PD-1-targeting therapy. According to the report, the first patient developed a fatal case of TB 2 months after receiving nivolumab for throat cancer. The second patient, who received pembrolizumab for skin cancer, was successfully treated for TB.

The researchers characterized the adaptive immune system in the surviving patient and found that “PD-1 blockade was followed by expansion of circulating (M. tuberculosis)-specific TH1 cells, but not (M. tuberculosis)-specific TH17 cells, CD8 T cells or increased antibody responses.”

According to the study, these results were consistent with previous data that suggested that boosting TH1 function with PD-1 blockade may increase the risk or severity of TB in humans and that screening for TB may be warranted.

“When cancer patients are treated with PD-1 blocking agents, it’s not only the immune response to the tumor that’s being impacted,” Barber said. “Although more studies are needed to conclusively show that tuberculosis is a potential adverse event directly resulting from PD-1 blockade, this study clearly indicates we should exercise caution when treating [M. tuberculosis]-infected individuals with this important new class of cancer drugs. It certainly seems warranted to screen for [M. tuberculosis] infection prior to initiating treatment of cancer patients with PD-1- or PD-L1-blocking drugs.”– by Caitlyn Stulpin

Disclosures: Barber reports receiving royalties from patents held relating to PD-1 blockade. All other authors report no relevant financial disclosures.