Hypofractionated stereotactic radiation therapy activates the peripheral immune response in operable stage I non-small-cell lung cancer

Abstract

It has been reported that in patients with operable stage I non-small cell lung cancer (NSCLC), overall survival (OS) is better in those who undergo hypofractionated stereotactic radiation therapy (HSRT) than in those who undergo surgery. However, the reason that HSRT has a better OS has not been fully explored. Here, we analyzed reconstitution kinetics in immune cells in the peripheral blood of NSCLC patients after HSRT. We found that HSRT increased the frequency of total T cells, especially the proportion of CD8+ T cells, but decreased the frequency of inhibitory Tregs. Intracellular staining showed that after HSRT, peripheral CD8+ T cells were transformed into activated T cells, which express high levels of TNF-α, IFN-γ, granzyme B and IL-2. HSRT also increased the production of IL-2, TNF-α, and IFN-γ but down-regulated the production of TGF-β in CD4+ T cells. The frequencies of naïve B cells and double-negative B cells were lower, while the proportions of MZ-like B cells, transitional B cells and plasmablast cells were higher after HSRT. Collectively, our results demonstrate that HSRT activates the peripheral immune response and indicate the dynamic variation in peripheral lymphocytes after HSRT, which is very important for optimizing combination treatments in clinical practice.

Expression and correlation of MALAT1 and SOX9 in non‐small cell lung cancer

“…NSCLC is still one of the most serious challenges facing to the global public health system . In China, the incidence and death rates of NSCLC are higher than other types of cancer, so NSCLC prevention and control strategies are very important issue for Chinese government . But the pathogenesis of NSCLC is very complex and has not been fully spelled out.…”

Relationship Between the Invasion of Lymphocytes and Cytokines in the Tumor Microenvironment and the Interval After Single Brachytherapy Hypofractionated Rradiotherapy and Conventional Fractionation Radiotherapy in Non-Small Cell Lung Cancer

“…The results of a comparative study with a 48 Gy/8 F or 48 Gy/6 F regimen for treatment by SBRT in NSCLC patients indicated that the levels of CD3 + T lymphocytes were slightly higher after SBRT, and they significantly increased at 3 weeks. The ratio of CD8 + T cells/CD3 + T cells increased significantly 3 weeks after SBRT [16]. In our study, we selected days 7 and 14 as the observation time windows, and it was possible to observe the high expression of tumor invasion lymphocytes and cytokines and the relationship between hypofractionated radiotherapy and tumor immune microenvironment.…”

“…The use of single brachytherapy hypofractionated radiotherapy (SBHFRT) in advanced NSCLC has rarely been reported in the literature, and there is no study on the relationship with immune cells. The results of our previous clinical studies have shown that the effective rate and 2-year overall survival after SBHFRT in patients with NSCLC were 92.3% and 67%, respectively, with a median survival period of 22.5 months [16]. Weather this outcome, in addition to the physical role of radioactive rays, is associated with immune cells and cytokines, especially anti-tumor lymphocytes and cytokines in the tumor microenvironment, is unknown.…”

“…Hypofractionated radiotherapy can stimulate the immune system. NSCLC patients undergoing SBRT have been reported to show increased proportions of CD8 + T cells and decreased levels of inhibitory tregs, with high expression levels of interferon-γ (INF-γ) [16]. In colon cancer, SBRT activates dendritic cells (DCs) and induces immune cell infiltration in tumors and migration of immune cells to tumors [15].…”

SMAC Mimetic Debio 1143 and Ablative Radiation Therapy Synergize to Enhance Antitumor Immunity against Lung Cancer

“…In patients with early-stage non-small cell lung cancer (NSCLC), delivery of highly conformal, high-dose ablative radiotherapy (ART) has demonstrated local control and survival rates that rival those of surgery (1). Aside from establishing local control of distant metastases, ART may, at times, contribute to systemic disease control through generating antitumor immunity by stimulating tumor antigen and cytokine release (2)(3)(4). As such, ART is also being increasingly utilized in patients with oligometa-static disease (5).…”