Abstract 744
Background
Immunotherapy, as a new treatment, has become an option after surgery, radiotherapy and chemotherapy, and its status is becoming more and more important. However, after PD-1/PD-L1 as the target of drug treatment, it is inevitable that the phenomenon of drug resistance will arise caused by the reduction of drug sensitivity. However, there is still no clear understanding of the mechanism of drug resistance to PD-1/PD-L1, which needs to be further explored.
Methods
Tissue biopsy was performed in patients with renal metastasis of lung squamous cell carcinoma, primary lung (P), renal metastases (M1), and PD-1-treated renal metastases (M2). Then, P1, M1, and M2 were sequenced by whole exome genome sequencing (WES) to construct a gene evolution map and neoantigens evolution tree. Furthermore, the genomic differences between P and M1, as well as between M1 and M2, were found, and the evolution of tumor was demonstrated.
Results
After WES, we found that 139 groups of mutations [tumor mutational burden (TMB)=4.48 mutations/MB] were detected in the most sensitive P for PD-1 treatment, and 67 neoantigens were expressed [tumor neoantigens burden (TNB)=2.16 neoantigens /MB]. Among them, 22 groups were P-specific mutations, and 9 kinds of P-specific neoantigens were expressed, among the unique neoantigens of P, 77.8% (7/9) of the neoantigens were not deleted by HLA (human leukocyte antigen). The sensitivity of patients with M1 to PD-1 was significantly lower than that of P. WES showed that a total of 201 mutations (TMB=6.48 mutation / MB) were detected in M1. Expression of 93 neoantigens (TNB=3.00 neoantigens / MB). Among them, 85 groups were M1-specific mutations, 35 kinds of M1-specific neoantigens were expressed, of which 51.4% (18/35) of the neoantigens had no deletion of HLA. M2 was resistant to PD-1, and a total of 135 mutations were detected in WES (TMB=4.35 mutation / MB), expressed 88 neoantigens (TNB=2.84 neoantigens / MB), 91 group was M1 and M2 common mutation, 43 group was M2 specific mutation. Expression of 21 kinds of M2 specific neoantigens. The HLA presenting these neoantigens was deleted.
Conclusions
The decrease of TMB, TNB and HLA expression are the important mechanisms of PD-1/PD-L1 resistance in non-small cell lung cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Henan Cancer Hospital.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
3630 - Results of phase 1 clinical trial of high doses of Seleno-L-methionine (SLM) in sequential combination with Axitinib in previously treated and relapsed clear cell renal carcinoma (ccRCC) patients
Presenter: Yousef Zakharia
Session: Poster Display session 3
Resources:
Abstract
2356 - Safety and Efficacy of CDX-014 , an Antibody-Drug Conjugate against T Cell immunoglobulin mucin-1 (TIM-1), in advanced Renal Cell Carcinoma
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
1028 - SPAZO2 (SOGUG): Outcomes and prognostic significance of IMDC intermediate prognosis subclassification in metastatic renal cell carcinoma (mRCC) in patients treated with 1st-line pazopanib (1stPz).
Presenter: Begona P. Valderrama
Session: Poster Display session 3
Resources:
Abstract
2293 - Effect of Antacid Intake on the Therapeutic Efficacy of Sunitinib (SUN) in Metastatic Renal Cell Carcinoma (mRCC) Patients (pts): a Sub-Analysis of the STAR-TOR Registry
Presenter: Katrin Schlack
Session: Poster Display session 3
Resources:
Abstract
1451 - Randomized phase 3 trial of avelumab + axitinib vs sunitinib as first-line treatment for advanced renal cell carcinoma: JAVELIN Renal 101 Japanese subgroup analysis
Presenter: Motohide Uemura
Session: Poster Display session 3
Resources:
Abstract
4399 - Overall and progression-free survival according to MSKCC scores in 1st line sunitinib treatment of metastatic renal cell carcinoma (mRCC)
Presenter: Jindrich Finek
Session: Poster Display session 3
Resources:
Abstract
1344 - Combination therapy with checkpoint inhibitors for first-line treatment of advanced renal cell carcinoma: A systematic review and meta-analysis of randomized controlled trials
Presenter: Kyaw Thein
Session: Poster Display session 3
Resources:
Abstract
3462 - A phase II trial of TKI induction followed by a randomized comparison between nivolumab or TKI continuation in renal cell carcinoma (NIVOSWITCH)
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract
5268 - Nivolumab (N) treatment beyond progression in a real-world cohort of patients (pts) with metastatic renal cell carcinoma (mRCC)
Presenter: Sophie Hans
Session: Poster Display session 3
Resources:
Abstract
4235 - First results of safety profile of nivolumab (NIVO) in combination with stereotactic body radiotherapy (SBRT) in II and III line of patients (pts) with metastatic renal cell carcinoma (mRCC) in NIVES Study
Presenter: Cristina Masini
Session: Poster Display session 3
Resources:
Abstract