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. 2021 Jun;12(11):1726-1734.
doi: 10.1111/1759-7714.13978. Epub 2021 May 4.

T-cell response to phytohemagglutinin in the interferon-γ release assay as a potential biomarker for the response to immune checkpoint inhibitors in patients with non-small cell lung cancer

Chisato Kamimaki  1 , Nobuaki Kobayashi  1 , Momo Hirata  1 , Kohei Somekawa  1 , Nobuhiko Fukuda  1 , Sousuke Kubo  1 , Seigo Katakura  1 , Shuhei Teranishi  2 , Keisuke Watanabe  1 , Nobuyuki Horita  1 , Yu Hara  1 , Masaki Yamamoto  2 , Makoto Kudo  2 , Hongmei Piao  3 , Takeshi Kaneko  1
Affiliations

T-cell response to phytohemagglutinin in the interferon-γ release assay as a potential biomarker for the response to immune checkpoint inhibitors in patients with non-small cell lung cancer

Chisato Kamimaki et al. Thorac Cancer. 2021 Jun.

Abstract

Background: Immune checkpoint inhibitors are a standard treatment for advanced lung cancer, although it remains important to identify biomarkers that can accurately predict treatment response. Immune checkpoint inhibitors enhance the antitumor T-cell response, and interferon-γ plays an important role in this process. Therefore, this study evaluated whether the number of interferon-γ-releasing peripheral T cells after phytohemagglutinin stimulation in the interferon-γ release assay might act as a biomarker for the response of non-small cell lung cancer to immune checkpoint inhibitor treatment.

Methods: Data were retrospectively collected regarding 74 patients with non-small cell lung cancer who had received immune checkpoint inhibitors. Pretreatment screening tests had been performed using the T-SPOT.TB assay, which quantifies the number of interferon-γ-releasing T cells (as immunospots) in response to phytohemagglutinin and tuberculosis-specific antigen stimulation. Clinical factors and the number of spots in the T-SPOT fields were evaluated for associations with patient outcomes. The median number of spots was used to categorize patients as having high or low values, and the two groups were compared.

Results: Relative to patients with a low ratio, patients with a high ratio of phytohemagglutinin/tuberculosis-specific antigen spots (i.e. more responsive T cells) had significantly better progression-free survival after immune checkpoint inhibitor treatment. When we only considered patients with negative T-SPOT results, a high number of phytohemagglutinin-stimulated spots corresponded to significantly longer progression-free survival.

Conclusion: The T-SPOT.TB assay can be used to quantify the number of immunospots in response to antigen stimulation, which may predict the response to immune checkpoint inhibitors in patients with non-small cell lung cancer.

Keywords: T-SPOT.TB; immune checkpoint inhibitor; interferon-γ; interferon-γ-releasing assay; lung cancer.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
Study flowchart. A total of 392 lung cancer patients was assessed, although we excluded 41 patients with small cell lung cancer, 186 patients without immune checkpoint inhibitor (ICI) treatment, and 91 patients who did not undergo T‐SPOT.TB testing. As one patient received two ICI regimens, we only considered the first ICI treatment. Thus, 74 patients were included
FIGURE 2
FIGURE 2
Kaplan–Meier analysis according to a low or high number of PHA/TBAg spots. Patients were divided according to the median numbers of spots for (a) PHA/ESAT‐6 and (b) PHA/CFP‐10. ESAT‐6, a tuberculosis‐specific antigen; CFP‐10, a tuberculosis‐specific antigen; PHA, phytohemagglutinin; NA, not available
FIGURE 3
FIGURE 3
Kaplan–Meier analysis according to a low or high number of PHA spots among patients with negative T‐SPOT results. Patients were divided according to the median number of phytohemagglutinin (PHA) spots. NA, not available
See this image and copyright information in PMC

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