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
2927 - Singapore Caregiver Quality Of Life Scale (SCQOLS): Turkish Validity and Reliability Study
Presenter: Nur Basak
Session: Poster Display session 3
Resources:
Abstract
5066 - Screening for Psicosocial Distress in recently diagnosed cancer patients
Presenter: Eva Baillès
Session: Poster Display session 3
Resources:
Abstract
6074 - Socio-demographic characteristics and quality of life analysis of cancer survivors followed at a Primary Care Center.
Presenter: Begona Grana Suarez
Session: Poster Display session 3
Resources:
Abstract
5129 - The adhesion in the screening measures in carrying patients of breast cancer and ovary hereditary and the relationship with the psychological aspects
Presenter: Melinda Concepcion
Session: Poster Display session 3
Resources:
Abstract
5635 - Assessment of emotional discomfort of oncological patients in the first nursing visit at Donostia University Hospital
Presenter: Elena Uranga
Session: Poster Display session 3
Resources:
Abstract
858 - A systematic review and meta-analysis of the distress thermometer for the screening of distress in Chinese patients with cancer
Presenter: Hui Hui Sun
Session: Poster Display session 3
Resources:
Abstract
4475 - Pharmacist and Nurse (PN) Led Melanoma Immunotherapy Clinic: Patient Experience Survey
Presenter: Dharmisha Chauhan
Session: Poster Display session 3
Resources:
Abstract
1871 - Phone Triage & Acute Review Clinics: The emerging role of the Oncology Specialist Nurse
Presenter: Fiona Barrett
Session: Poster Display session 3
Resources:
Abstract
5193 - Patient reported outcomes during immunotherapy: symptom burden in daily clinical practice
Presenter: José Koldenhof
Session: Poster Display session 3
Resources:
Abstract
2453 - Factors related to hospital length of stay, re-admissions and unplanned care for patients with cancer, an on-going study
Presenter: Helena Ullgren
Session: Poster Display session 3
Resources:
Abstract