Abstract
Purpose
Undifferentiated pleomorphic sarcoma (UPS) is associated with poor prognosis. Recently, signal regulatory protein alpha (SIRPα), which is the immune checkpoint of macrophages, and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), which is the immune checkpoint of T cells and natural killer cells, have been considered as potential targets for cancer immunotherapy. This study aimed to assess the value of SIRPα and TIGIT as prognostic factors of UPS.
Materials and methods
The cBio Cancer Genomics Portal was used to analyze mRNA expression data of 50 UPS cases in the Cancer Genome Atlas. We retrieved 49 UPS cases and performed immunohistochemistry (IHC) to detect programmed death ligand 1 (PD-L1), SIRPα, CD68, CD163, TIGIT, CD155, and CD8.
Results
SIRPα was positively associated with CD163 (Pearson’s r = 0.51, p = 0.0002) as per open access data and IHC of the cohort (p = 0.002), which revealed that SIRPα-positive macrophage infiltration was higher in UPS cells with ≥ 1% PD-L1 expression than that in UPS cells with < 1% PD-L1 expression (p = 0.047). TIGIT was positively correlated with PD-L1 (r = 0.54, p < 0.0001) and CD8A (r = 0.98, p < 0.0001). In 35 of 49 cases, IHC revealed high levels of TIGIT expression on tumor cells. Furthermore, TIGIT expression on tumor cells was negatively correlated with CD155-positive (p = 0.0144) and CD8-positive (p = 0.0487) cell infiltration. Survival analysis showed that the high degree of SIRPα-positive macrophage infiltration was associated with poor overall survival and metastasis (p < 0.0001, p = 0.0006, respectively).
Conclusion
SIRPα-positive macrophages infiltrated UPS cells, which predicted poor prognosis. High TIGIT expression on tumor cells was associated with decreased levels of tumor-infiltrating macrophages in UPS.
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Abbreviations
- SIRPα:
-
Signal regulatory protein alpha
- TIGIT:
-
T cell immunoreceptor with immuoglobulin and immunoreceptor tyrosine-based inhibition motif domains
- UPS:
-
Undifferentiated pleomorphic sarcoma
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Acknowledgements
We appreciate the English language review by Enago and thank Mrs. M. Nakamizo and Mrs. M. Tomita at Kyushu University for technical assistance. We also thank Dr. I. Kinoshita, Dr. Y. Yamada, and Dr. H. Yamamoto at Kyushu University Hospital.
Funding
This work was supported by the Japan Society for the Promotion of Science KAKENHI (Grant number [19H03444] and [21K20805]).
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All authors contributed to the study conception and design. SI, TI, KK, YN, and YO designed this study and wrote the manuscript. SI, TI, KK, YT, KK, YI, YS, EM and YM performed the experiments. TF, NS, EM and YM collected the clinical data. SI, TI, KK, and YO performed histological re-evaluation of the samples and confirmed the diagnosis. YO supervised the experiments.
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This study was approved by the Kyushu University Committee of Bioethics (approval no. 29–429 and 29–625; 2017).
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Ishihara, S., Iwasaki, T., Kohashi, K. et al. Clinical significance of signal regulatory protein alpha and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain expression in undifferentiated pleomorphic sarcoma. J Cancer Res Clin Oncol 149, 2425–2436 (2023). https://doi.org/10.1007/s00432-022-04078-y
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DOI: https://doi.org/10.1007/s00432-022-04078-y