Abstract 3747
Background
A recent clinical study indicated that anti-programmed death-ligand 1 antibody durvalumab consolidation therapy for patients with non-small cell lung cancer (NSCLC) who received chemoradiotherapy (CRT) resulted in robust improvement in progression-free survival (PFS) and prevented distant metastasis. It has been demonstrated that cluster of differentiation (CD)8+ T cell priming is facilitated by immunogenic cancer cell death by radiotherapy. On the other hand, accumulating evidence indicates that CD4+ T cells are required for effective antitumor T cell responses because CD4+ T cells help regulate priming, migration, invasive potential, and antitumor killing activity of cytotoxic lymphocytes. It remains uncertain how thoracic CRT evokes antitumor T cell immune responses in patients with NSCLC.
Methods
The present study comprised 56 consecutive patients with locally advanced NSCLC who received curative CRT or thoracic radiotherapy in the Saitama Medical University International Medical Center. Twenty-two patients received durvalumab consolidation therapy after CRT. Peripheral blood samples were collected before and sequentially after radiotherapy. Peripheral blood mononuclear cells were analyzed using LSR FortessaTM and CyTOFTM.
Results
After radiotherapy, significant increases in the percentages of CD62Llow CD4+ T cells and human leukocyte antigen-DR+ myeloid dendritic cells were observed. Mass cytometry analysis revealed that the increased CD62Llow CD4+ T cells consisted of T-bet+ CXCR3+ CD27- type 1 T helper (Th1) cells. Programmed death-1, lymphocyte-activation gene-3, and inducible T-cell costimulator expression in CD62Llow CD4+ T cells also significantly increased. Interestingly, CD62Llow CD4+ T cells initiated decreasing 4 weeks after radiotherapy in half of the patients.
Conclusions
Radiotherapy induced myeloid dendritic cell activation and subsequent increase in T-bet+ CXCR3+ CD27- CD62Llow CD4+ Th1 cells. The correlation between CD4+ T-cell responses and clinical responses of durvalumab is under examination.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
O. Yamaguchi: Research grant / Funding (institution): Nihon Medi-Physics Co., Ltd.; Speaker Bureau / Expert testimony: Ono Pharmaceutical; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: AstraZeneca. A. Mouri: Speaker Bureau / Expert testimony: Ono Pharmaceutical; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Boehringer Ingelheim. K. Kobayashi: Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Taiho Pharmaceutical Company; Speaker Bureau / Expert testimony: Ono Pharmaceutical Company. K. Kaira: Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Ono Pharmaceutical Company; Speaker Bureau / Expert testimony: Eli Lilly. H. Kagamu: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Eli Lilly; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical. All other authors have declared no conflicts of interest.
Resources from the same session
5638 - Incidence of Vascular Thromboembolism Events in Cancer Patients Receiving Immunotherapy: A Single Institution Experience.
Presenter: Laura Gutiérrez Sainz
Session: Poster Display session 1
Resources:
Abstract
5182 - High Incidence of Venous Thromboembolic Events (VTE) in Patients with Diffuse Large B-Cell Lymphoma.
Presenter: Alaa Abufara
Session: Poster Display session 1
Resources:
Abstract
1504 - Weight Loss over Time in Non-Small Cell Lung Cancer: Results from a Landmark Analysis of 800+ Prospectively-Treated Patients
Presenter: Jennifer Le-rademacher
Session: Poster Display session 1
Resources:
Abstract
3972 - The prognostic significance of preoperative nutritional status in resected pancreatic ductal adenocarcinoma (PDAC).
Presenter: Salvatore Paiella
Session: Poster Display session 1
Resources:
Abstract
2313 - Impact of Timing and Technique of Gastrostomy Placement on the Outcome of Patients (pts) with Head and Neck Cancer (HNC)
Presenter: M Julia Lostes Bardaji
Session: Poster Display session 1
Resources:
Abstract
5219 - Clinical & nutritional determinants of quality of life in patients with incurable cancer
Presenter: Louise Daly
Session: Poster Display session 1
Resources:
Abstract
4075 - Loss of skeletal muscle mass during palliative chemotherapy is a poor prognostic factor in patients with advanced gastric cancer
Presenter: In Gyu Hwang
Session: Poster Display session 1
Resources:
Abstract
4159 - Impact of nutritional derangement on treatment outcome in advanced non-small-cell lung cancer (A-NSCLC) patients (pts).
Presenter: Ilaria Trestini
Session: Poster Display session 1
Resources:
Abstract
1210 - Sarcopenia and pretreatment anemia as prognostic factors for patients with localized muscle invasive bladder cancer treated by neoadjuvant chemotherapy and radical cystectomy
Presenter: Emilien Billon
Session: Poster Display session 1
Resources:
Abstract
2490 - Gender effect on the pharmacokinetics (PK) and pharmacodynamics (PD) of anamorelin (ANAM) in healthy volunteers and cancer patients with cachexia
Presenter: Stein Kaasa
Session: Poster Display session 1
Resources:
Abstract