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
4021 - Prospective pathological experience with research biopsies in the context of clinical trials at Vall d’Hebron Institute of Oncology
Presenter: Paolo Nuciforo
Session: Poster Display session 3
Resources:
Abstract
5603 - Development of a comprehensive next-generation targeted sequencing assay for detection of gene-fusions in solid tumors
Presenter: Vinay Mittal
Session: Poster Display session 3
Resources:
Abstract
4952 - Next-generation sequencing for better treatment strategy of cancer of unknown primary (CUP)
Presenter: Kang Kook Lee
Session: Poster Display session 3
Resources:
Abstract
4590 - Circulating-free DNA analysis from long-term surviving metastatic colorectal cancer patients undergoing surgery for resectable disease.
Presenter: Michele Ghidini
Session: Poster Display session 3
Resources:
Abstract
3696 - Ultra-sensitive detection of circulating tumor DNA identifies patients in high risk of recurrence in early stages melanoma
Presenter: Filip Janku
Session: Poster Display session 3
Resources:
Abstract
4295 - Identification of the founder BRCA1 mutation c.4117G>T (p.Glu1373*) recurring in Abruzzo and Lazio regions of Central Italy and predisposing to breast/ovarian and BRCA1-related cancers
Presenter: Daniela Di Giacomo
Session: Poster Display session 3
Resources:
Abstract
2214 - Enzalutamide (ENZA) and Apalutamide (APA) In vitro chemical reactivity studies and Activity in a Mouse Drug Allergy Model (MDAM)
Presenter: Mausumee Guha
Session: Poster Display session 3
Resources:
Abstract
5044 - Influence of genetic variation in COMT on cisplatin-induced nephrotoxicity in cancer patients.
Presenter: Bram Agema
Session: Poster Display session 3
Resources:
Abstract
3293 - Cardioprotective and anti-inflammatory effects of Empagliflozin during treatment with Doxorubicin: a cellular and preclinical study
Presenter: Vincenzo Quagliariello
Session: Poster Display session 3
Resources:
Abstract
3324 - Breast Cancer Organoids Model Treatment Response of HER2 Targeted Therapy in HER2-mutant Breast Cancer
Presenter: Xuelu Li
Session: Poster Display session 3
Resources:
Abstract