Abstract 4572: The induction of PD-L1 positive immune cells and CD8-positive T lymphocytes by neoadjuvant chemoradiotherapy for rectal cancer
Authors: Yamashita Kimihiro , Nakagawa Akio , Tanaka Tomoko , Arimoto Akira , Fukuoka Eiji , Sugita Yutaka , Mukohyama Junko , Dalerba Piero , Hasegawa Hiroshi , Matsuda Takeru , Suzuki Satoshi , Kakeji Yoshihiro 
Published: August 2018

Abstract
Background; Immunotherapy, particularly blockade of programmed cell death-1 (PD-1) has shown unprecedented success in treating various types of cancers. In recent clinical trial of PD-1 blockade, clinicians focused on the characteristics of metastatic colorectal cancer patients with MSI-H (microsatellite instability- high) tumor associated with somatic hypermutation and confirmed a benefit of this immunotherapy in the disease. On the other hand, for MSS patients who account for most of colorectal cancer patient, new immunological strategies are needed. From before, radiation therapy is expected as an approach to overcome this relative resistance across colorectal cancers. Some reports on the relationship between tumor immunological microenvirment and irradiation have also been reported. Based on these findings, we examined a tumor immunological microenvironment of rectal cancer performed by chemoradiotherapy with immunohistochemical analysis of biopsy and surgical specimens.
Methods; From January 2005 to December 2016, 77 lower rectal cancer cases with cT3-4 or cN (+) were surgically treated in our institution and enrolled and 68 were eligible for this study. Immunohistochemistry of PD-L1, CD8, and CD163 was performed on biopsy specimens and surgically resected specimens of all cases, and their changes of expression before and after treatment were examined. We also examined the relationship between the expression of these tumor immunity-related factors and clinicopathological factors and prognosis.
Results; There were 44 cases in which NACRT was performed (NA group) and 24 cases in which surgery alone was performed (S group). In the S group, there was no significant change in the infiltration of PD-L1 positive immune cells (PD-L1+IC) nor CD8 positive tumor-infiltrating lymphocytes (CD8+TIL) before and after treatment, but in the NA group, the infiltrations of them were significantly increased (p = 0.038 and p = 0.0027, respectively). Although no PD-L1 positive tumor cells (PD-L1+TC) were observed in the biopsy specimens, there were 5 cases in which PD-L1+TC were observed in the surgically resected specimens, and all of which were cases of NACRT group (not significant). In multivariate analysis, low infiltration of PD-L1+IC (p = 0.033) was revealed as poor prognostic factor in overall survival, and low infiltration of PD-L1+IC (p = 0.041) and CD8+TIL (p = 0.0094) were identified as poor prognostic factors in disease-free survival.
Conclusion; The infiltration of PD-L1+IC and CD8+TIL was induced by NACRT. The presence of PD-L1+IC in the tumor tissue was revealed to improve the prognosis of rectal cancer. In NACRT for rectal cancer, PD-1 inhibitor combination therapy should be introduced to tumors with PD-L1 positive IC.
Citation Format: Kimihiro Yamashita, Akio Nakagawa, Tomoko Tanaka, Akira Arimoto, Eiji Fukuoka, Yutaka Sugita, Junko Mukohyama, Piero Dalerba, Hiroshi Hasegawa, Takeru Matsuda, Satoshi Suzuki, Yoshihiro Kakeji. The induction of PD-L1 positive immune cells and CD8-positive T lymphocytes by neoadjuvant chemoradiotherapy for rectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4572.