Abstract
The expression of programmed cell death 1 ligand 1 (PD-L1) and interferon-γ (IFN-γ) is of great interest for the development of chemoradiotherapy and immune checkpoint inhibitor treatments. Patients with nodal metastasis (pN+) tend to have a poor prognosis, even after neoadjuvant chemoradiotherapy (neoCRT) and surgical treatment. In this study, we examined the roles of tumor PD-L1 and IFN-γ before and after neoCRT in locally advanced rectal cancer (LARC) patients. Our results demonstrate that patients with high PD-L1 expression in post-neoCRT tissues exhibit improved 5-year disease-free survival (DFS) and overall survival (OS) compared with those with low PD-L1 expression (p < 0.001). Furthermore, in the pN+ population, patients with high PD-L1 expression in post-neoCRT tissues exhibit improved 5-year DFS and OS. PD-L1 and IFN-γ upregulation increased in tumor tissues after neoCRT, and patients with high PD-L1 and high IFN-γ exhibit improved 5-year DFS and OS (p = 0.04 and p = 0.001, respectively). To the best of our knowledge, this study is the first to demonstrate that PD-L1 upregulation in a pN+ cohort correlates with improved prognosis, which is similar to that in patients without nodal metastasis. Moreover, this study verified that PD-L1 and IFN-γ were upregulated by neoCRT treatment in LARC patients and demonstrated that neoCRT may be useful not only for immune checkpoint inhibitor treatment but also for reinvigorating preexisting anti-cancer immunity.
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Abbreviations
- CRC:
-
Colorectal cancer
- DAMPs:
-
Danger-associated molecular patterns
- DFS:
-
Disease-free survival
- ICB:
-
Immune checkpoint blockade
- ICD:
-
Immunogenic cell death
- IFN-γ:
-
Interferon-γ
- LARC:
-
Locally advanced rectal cancer
- MSI:
-
Microsatellite instability
- neoCRT:
-
Neoadjuvant chemoradiotherapy
- OS:
-
Overall survival
- pCR:
-
Pathologic complete response
- PD-1:
-
Programmed cell death 1 receptor
- PD-L1:
-
Programmed cell death 1 ligand 1
- pN stage:
-
Pathologic lymph node stage
- TILs:
-
Tumor-infiltrating lymphocytes
- TMA:
-
Tissue microarray
- TRG:
-
Tumor regression grade
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Funding
This study was supported by grants from China Medical University Hospital [DMR-107-103 (Taiwan) and DMR-CELL-17022 (Taiwan)], Ministry of Science and Technology (MOST 107-2314-B-039 -027 -MY3, Taiwan), Ministry of Health, and Welfare (MOHW107-TDU-B-212-123004, Taiwan), and Health and welfare surcharge of tobacco products, China Medical University Hospital Cancer Research Center of Excellence (MOHW107-TDU-B-212-114024, Taiwan).
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C-YH and S-FC conducted and performed the experiments; WT-LC, T-WK and T-WC enrolled the LARC patients and performed IHC evaluation; Y-SY and Y-CL performed the statistical analysis; S-FC and KSCC supervised this study; C-YH, S-FC, and KSCC analyzed the data and wrote the manuscript. All authors read and approved the final manuscript version.
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Chiang, SF., Huang, CY., Ke, TW. et al. Upregulation of tumor PD-L1 by neoadjuvant chemoradiotherapy (neoCRT) confers improved survival in patients with lymph node metastasis of locally advanced rectal cancers. Cancer Immunol Immunother 68, 283–296 (2019). https://doi.org/10.1007/s00262-018-2275-0
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DOI: https://doi.org/10.1007/s00262-018-2275-0