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

Shin Ishihara, Takeshi Iwasaki, Kenichi Kohashi, Kengo Kawaguchi, Yu Toda, Toshifumi Fujiwara, Nokitaka Setsu, Makoto Endo, Yoshihiro Matsumoto, Yasuharu Nakashima, Yoshinao Oda

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalJournal of Cancer Research and Clinical Oncology
DOIs
Publication statusAccepted/In press - 2022

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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