Date Published: February 26, 2019
Publisher: Public Library of Science
Author(s): Tetsuro Tominaga, Takashi Akiyoshi, Noriko Yamamoto, Senzo Taguchi, Seiichi Mori, Toshiya Nagasaki, Yosuke Fukunaga, Masashi Ueno, Aamir Ahmad.
Inhibition of the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis in combination with radiotherapy may be a promising approach to treat cancer. In the present study, we aimed to evaluate serum soluble PD-1/PD-L1 levels in patients with advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT).
Serum soluble PD-L1 and PD-1 levels were measured using an enzyme-linked immunosorbent assay before and after CRT in 117 patients with low rectal cancer. Changes in the levels of sPD-L1/PD-1 after CRT, and the correlation between sPD-L1/PD-1 level and clinicopathological characteristics or disease-free survival (DFS) were evaluated.
sPD-L1 levels significantly increased after CRT (p < 0.0001), whereas sPD-1 levels did not change significantly (p = 0.1050). High sPD-L1 before CRT was significantly associated with younger age (p = 0.044), and after CRT, with lymphovascular invasion (p = 0.021). High sPD-1 before and after CRT was significantly associated with a longer distance of the tumor from the anal verge (both p < 0.001). There was no correlation between sPD-L1 level and local PD-L1 expression on stromal immune cells. High sPD-L1 level after CRT tended to be associated with worse DFS (p = 0.0752). The multivariate analysis could not demonstrate an independent association for sPD-L1 levels after CRT with DFS. Significant increase of sPD-L1 levels after CRT suggests that anti-PD-L1 therapy might be a potential treatment strategy in combination with CRT in advanced rectal cancer.
Neoadjuvant chemoradiotherapy (CRT) is the standard of care for locally advanced rectal cancer. Several randomized, controlled trials (RCTs) have demonstrated that neoadjuvant CRT reduces the local recurrence rate in these patients [1–4]. However, CRT has no significant effect on long-term outcome, and distant metastasis is still the dominant cause of death after CRT. Alternative strategies incorporating systemic chemotherapy before or just following neoadjuvant CRT have been investigated in some clinical trials, but there is insufficient evidence to show that such strategies reduce metastatic risk as compared with conventional CRT [5, 6]. Therefore, novel treatment strategies are necessary to improve the oncological outcomes in patients with advanced rectal cancer.
Table 1 shows the clinicopathological characteristics of the 117 patients enrolled in the present study. The median distance of the tumor from the anal verge was 40 mm (range, 0 to 80 mm). Most of the patients were diagnosed as T3.
In the present study, we showed that sPD-L1, but not sPD-1, significantly increased after CRT. Patients with high sPD-L1 levels after CRT showed a trend toward worse DFS than those with low sPD-L1 levels. This is the first study to demonstrate the change in sPD-L1 levels following CRT in patients with advanced rectal cancer.