Abstract 6127
Background
Tumor mutation burden (TMB) and T cell receptor (TCR) diversity have been suggested as predictive biomarkers in cancer immunotherapy. It is not clear how chemotherapy influences TMB, and how TMB or clinical factors correlate with TCR clonality. The aim of this study is to investigate the relationship between TMB and TCR clonality and to provide suggestions for patient selection and the opportunity to start immunotherapy in East Asian late-stage lung cancer patients with first-line chemotherapy.
Methods
43 NSCLC patients and 18 SCLC patients with no TKI-related driver gene (EGFR, ALK, ROS1, RET, BRAF, C-MET) mutations were enrolled in this study. Genomic variations and TMB were determined with lung cancer tissue by whole-exome sequencing (WES). TCR sequencing was also performed with peripheral blood samples. Sequencing data were analyzed with R packages and statistics analysis was performed with SPSS 20 software. P ≤ 0.05 was regarded as statistically significant.
Results
The mutation spectrums were changed dramatically after chemotherapy in NSCLC patients. Chemotherapy appeared to cause decreases in the positive detection rate of mutated genes. Significant decrease in TMB from mean value of 3.67 to 1.95 were observed after chemotherapy in these NSCLC patients (p = 0.05), and patients can be dichotomized based on TMB decrease extent. The relationship between TCR clonality and TMB or clinical factors were also explored in NSCLC and SCLC patients. The number of TCR clones was not correlated with TMB, gender, age, metastasis, lung cancer subtype or therapeutic response (p > 0.05). However, it was dramatically higher in patients with smoking history than those with no smoking history (p = 0.01).
Conclusions
This study suggested that chemotherapy could alter the genomic profiles and TMB dramatically. Patients with decreased TMB after the first-line chemotherapy may be less likely to benefit from immunotherapy. Non-smokers with higher TCR diversity than smokers may be more likely to benefit from immunotherapy. Since the number of TCR clones was not correlated with TMB, it is still worth investigating whether TMB or TCR clonality, or both combined is a better predictive biomarker for immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study was supported in part by a grant from National Natural Science Foundation of China (81802255), Shanghai Pujiang Program (17PJD036) and a grant from Shanghai Municipal Commission of Health and Family Planning Program (20174Y0131). National key research & development project (2016YFC0902300). Major disease clinical skills enhancement program of three-year action plan for promoting clinical skills and clinical innovation in municipal hospitals, Shanghai Shen Kang Hospital Development Center Clinical Research Plan of SHDC (16CR1001A). The fundamental research funds for the central universities.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3073 - 1 patient 3 different advance Ca nurse’s roles: symptom management&continuum care through a joint approach in a clinical case
Presenter: Catarina Almeida
Session: Poster Display session 3
Resources:
Abstract
4527 - Identification of malnutrition risk factors in patients with cancer in the first nursing visit
Presenter: Amaia Valverde
Session: Poster Display session 3
Resources:
Abstract
2904 - Engaging Cancer Survivors, Healthcare Providers and Advocates in The Development of a Colorectal Cancer Survivorship Information Resource: A Participatory Action Research Study
Presenter: Amanda Drury
Session: Poster Display session 3
Resources:
Abstract
3435 - Medical nurses’ experiences of the care-needs of adult patients with a primary brain tumour
Presenter: Jamila Mohammed
Session: Poster Display session 3
Resources:
Abstract
857 - Feasibility and acceptability of a mHealth intervention to increase colonoscopy uptake among Chinese first-degree relatives: a pilot cluster randomized controlled trial
Presenter: Yang Bai
Session: Poster Display session 3
Resources:
Abstract
1087 - Cancer patient participation and compliance in microbiome sample collection: an oncology research nurse’s experience
Presenter: Julie Malo
Session: Poster Display session 3
Resources:
Abstract
2783 - Implementing Digital Individual Care plans for Patients with Head and Neck cancer- Challenges and opportunities
Presenter: Helena Ullgren
Session: Poster Display session 3
Resources:
Abstract
1152 - The Effect of the Short-term and Long-term Compassion Fatigue Resiliency Program on the Quality of Life, Perceived Stress and Psychological Resilience of Oncology-Hematology Nurses
Presenter: Tugba Pehlivan
Session: Poster Display session 3
Resources:
Abstract
1172 - Competing risk analyses of overall survival and cancer-specific survival in patients with orbital rhabdomyosarcoma after surgery: a large cohort study
Presenter: Yu Zhang
Session: Poster Display session 3
Resources:
Abstract
5949 - Communication of genetic information to family members in hereditary cancers and healthcare providers’ role
Presenter: Carla Pedrazzani
Session: Poster Display session 3
Resources:
Abstract