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
5105 - Fresh blood Immune cell monitoring in patients treated with nivolumab in the GETUG-AFU26 NIVOREN study: association with toxicity and treatment outcome
Presenter: Aude DESNOYER
Session: Poster Display session 3
Resources:
Abstract
1877 - Advanced clear-cell renal cell carcinoma (accRCC): association of microRNAs (miRNAs) with molecular subtypes, mRNA targets and outcome.
Presenter: Annelies Verbiest
Session: Poster Display session 3
Resources:
Abstract
5543 - Prior tyrosine kinase inhibitors (TKI) and antibiotics (ATB) use are associated with distinct gut microbiota ‘guilds’ in renal cell carcinoma (RCC) patients
Presenter: Valerio Iebba
Session: Poster Display session 3
Resources:
Abstract
2689 - mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
Presenter: Cristina Suarez Rodriguez
Session: Poster Display session 3
Resources:
Abstract
3069 - Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in Advanced Renal Cell Carcinoma (RCC)
Presenter: Aly-Khan Lalani
Session: Poster Display session 3
Resources:
Abstract
5089 - Finding the Right Biomarker for Renal Cell Carcinoma (RCC): Nivolumab treatment induces the expression of specific peripheral lymphocyte microRNAs in patients with durable and complete response.
Presenter: Lorena Incorvaia
Session: Poster Display session 3
Resources:
Abstract
2594 - Algorithms derived from quantitative pathology can be a gatekeeper in patient selection for clinical trials in localised clear cell renal cell carcinoma (ccRCC)
Presenter: In Hwa Um
Session: Poster Display session 3
Resources:
Abstract
2566 - High baseline blood volume is an independent favorable prognostic factor for overall and progression-free survival in patients with metastatic renal cell carcinoma
Presenter: Aska Drljevic-nielsen
Session: Poster Display session 3
Resources:
Abstract
2675 - Impact of estimand selection on adjuvant treatment outcomes in renal cell carcinoma (RCC)
Presenter: Daniel George
Session: Poster Display session 3
Resources:
Abstract
1541 - TERT gene fusions characterize a subset of metastatic Leydig cell tumors
Presenter: Bozo Kruslin
Session: Poster Display session 3
Resources:
Abstract