3747 - Effector CD4+ T-cell induction by thoracic radiotherapy for patients with NSCLC

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 Fortessa^TM and CyTOF^TM.

Results

After radiotherapy, significant increases in the percentages of CD62L^low CD4⁺ T cells and human leukocyte antigen-DR⁺ myeloid dendritic cells were observed. Mass cytometry analysis revealed that the increased CD62L^low 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 CD62L^low CD4⁺ T cells also significantly increased. Interestingly, CD62L^low 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^- CD62L^low 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.