| Title |
The combination of anti-KIR monoclonal antibodies with anti-PD-1/PD-L1 monoclonal antibodies could be a critical breakthrough in overcoming tumor immune escape in NSCLC
|
|---|---|
| Published in |
Drug Design, Development and Therapy, April 2018
|
| DOI | 10.2147/dddt.s163304 |
| Pubmed ID | |
| Authors |
Yayi He, Sangtian Liu, Jane Mattei, Paul A Bunn, Caicun Zhou, Daniel Chan |
| Abstract |
The anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) monoclonal antibody has a good effect in the treatment of non-small cell lung cancer (NSCLC), but not all PD-1/PD-L1 positive patients can get benefit from it. Compensatory expression of other immune checkpoints may be correlated with the poor efficacy of anti-PD-1/PD-L1 monoclonal antibodies. The inhibitory human leukocyte antigen (HLA)/killer cell Ig-like receptor (KIR) can effectively block the killing effect of natural killer (NK) cells on tumors. Our previous studies have confirmed that high expression of KIR was correlated with poor prognosis of NSCLC. Inhibitory KIR expression was positively correlated with the expression of PD-1. The expressions of KIR 2D (L1, L3, L4, S4) (BC032422/ADQ31987/NP_002246/NP_036446, Abcam) and PD-1 (NAT 105, Cell marque) proteins was assessed by immunohistochemistry. The expression of inhibitory KIR in tumor cells or tumor infiltrating lymphocytes (TILs) is associated with PD-1 expression. Among PD-1 positive patients, 76.3% were KIR 2D (L1, L3, L4, S4) positive on tumor cells, and 74.6% were KIR 2D (L1, L3, L4, S4) positive on TILs. We compared the expression of inhibitory KIR before and after treatment with nivolumab in 11 patients with NSCLC. We found that five (45.5%) patients had positive expression of inhibitory KIR in tumor tissue after being treated with anti-PD-1 monoclonal antibodies, two of whom exhibited a significant increase in expression of inhibitory KIR, and three showed no change. PD-1 expression was correlated with KIR 2D (L1, L3, L4, S4) on tumor cells or TILs. The resistance to anti-PD-1 monoclonal antibody treatment might be related to KIR. The inhibitory HLA/KIR could combine with the PD-1/PD-L1 signaling pathway negatively regulating NSCLC tumor immunity. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 37 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 9 | 24% |
| Student > Bachelor | 5 | 14% |
| Student > Ph. D. Student | 5 | 14% |
| Student > Postgraduate | 3 | 8% |
| Researcher | 2 | 5% |
| Other | 4 | 11% |
| Unknown | 9 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 19% |
| Agricultural and Biological Sciences | 6 | 16% |
| Immunology and Microbiology | 5 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 11% |
| Biochemistry, Genetics and Molecular Biology | 4 | 11% |
| Other | 2 | 5% |
| Unknown | 9 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 May 2018.
All research outputs
#20,663,600
of 25,382,440 outputs
Outputs from Drug Design, Development and Therapy
#1,436
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Outputs of similar age
#268,557
of 343,807 outputs
Outputs of similar age from Drug Design, Development and Therapy
#42
of 62 outputs
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