PT  - JOURNAL ARTICLE
AU  - Diego A Lema
AU  - Ewa Jankowska-Gan
AU  - Nan Sethakorn
AU  - William Burlingham
AU  - Ticiana Leal
TI  - Identification of PD1-mediated regulation of antitumor antigen response in patients with NSCLC using the trans vivo DTH assay
AID  - 10.1136/jitc-2019-000152
DP  - 2020 Jun 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e000152
VI  - 8
IP  - 1
4099  - http://jitc.bmj.com/content/8/1/e000152.short
4100  - http://jitc.bmj.com/content/8/1/e000152.full
SO  - J Immunother Cancer2020 Jun 01; 8
AB  - Objectives Emerging evidence has shown a role for tumor antigen-specific regulation in cancer. Identifying individuals with pre-existing regulatory responses may be key to understand those who are more likely to respond to Programmed Death-1 (PD-1) or PD-1 Ligand 1 (PD-L1) checkpoint blockade. We hypothesized that a functional assay could identify the role of PD-1/PD-L1 interactions on tumor-specific immune cells in the peripheral blood in patients with advanced non-small-cell lung cancer (NSCLC).Methods We performed the trans vivo delayed-type hypersensitivity assay to identify the role of PD-1/PD-L1-mediated tumor-specific immune regulation in ten patients with advanced NSCLC.Results The majority of patients had PD-1-mediated anergic immune responses towards their tumor antigens. Eight out of nine of these patients did not respond to their own tumor antigens but responded in the presence of anti-PD-1 antibody (‘PD-1 anergy’ phenotype). A minority (3/9) also had ‘active’ PD-1-mediated immune suppressive regulatory responses. Our results suggest that PD-1-anergy is a common feature of NSCLC immune responses, whereas PD-1-mediated immune suppression is present only in a minority of patients. The latter was associated with poor clinical outcomes in our sample.Conclusions Overall, our results indicate that bystander suppression or the ‘anergy-only’ phenomenon may be novel biomarkers in NSCLC and suggest prediction value based on these phenotypes.