Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2013 Dec 11;8(12):e82870.
doi: 10.1371/journal.pone.0082870. eCollection 2013.

Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas

Jung Ryul Kim  1 , Young Jae Moon  1 , Keun Sang Kwon  2 , Jun Sang Bae  3 , Sajeev Wagle  3 , Kyoung Min Kim  3 , Ho Sung Park  3 , Ho Lee  4 , Woo Sung Moon  3 , Myoung Ja Chung  3 , Myoung Jae Kang  3 , Kyu Yun Jang  3
Affiliations
Clinical Trial

Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas

Jung Ryul Kim et al. PLoS One. .

Abstract

Recently, the possibility of PD1 pathway-targeted therapy has been extensively studied in various human malignant tumors. However, no previous study has investigated their potential application for soft-tissue sarcomas (STS). In this study, we evaluated the clinical impact of intra-tumoral infiltration of PD1-positive lymphocytes and PD-L1 expression in tumor cells in 105 cases of STS. Intra-tumoral infiltration of PD1-positive lymphocytes and PD-L1 expression were seen in 65% and 58% of STS, respectively. Both PD1-positivity and PD-L1 expression were significantly associated with advanced clinicopathological parameters such as higher clinical stage, presence of distant metastasis, higher histological grade, poor differentiation of tumor, and tumor necrosis. Moreover, both PD1-positivity and PD-L1 positivity were independent prognostic indicators of overall survival (OS) and event-free survival (EFS) of STS by multivariate analysis. In addition, the combined pattern of PD1- and PD-L1-positivity was also an independent prognostic indicator for OS and EFS by multivariate analysis. The patents with a PD1(+)/PD-L1(+) pattern had the shortest survival time. In conclusion, this study is the first to demonstrate that the infiltration of PD1 positive lymphocytes and PD-L1 expression in STS cells could be used as novel prognostic indicators for STS. Moreover, the evaluation of PD1- and PD-L1-positivity in STS is also available as possible criteria for selection of patients suitable for PD1-based immunotherapy.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Immunohistochemical expression of PD1 and PD-L1 in various soft-tissue sarcomas.
Arrows indicate PD1 positive lymphocytes. Original magnification, x400.
Figure 2
Figure 2. Kaplan-Meier survival analysis in soft-tissue sarcomas.
Overall survival and event-free survival according to tumor stage (A), intra-tumoral infiltration of PD1-positive lymphocytes (B), expression of PD-L1 (C), and the combined expression pattern of PD1 and PD-L1 (PD1/PD-L1) (D).
Figure 3
Figure 3. Kaplan-Meier survival analysis in the low and high stage subgroup of soft-tissue sarcomas.
Overall survival and event-free survival according to the combined expression pattern of PD1 and PD-L1 (PD1/PD-L1) in low stage (stage I and II) (A) and high stage (stage III and IV) (B) subgroup of soft-tissue sarcomas.
See this image and copyright information in PMC

References

    1. Nishimura H, Honjo T (2001) PD-1: an inhibitory immunoreceptor involved in peripheral tolerance. Trends Immunol 22: 265-268. doi:10.1016/S1471-4906(01)01888-9. PubMed: 11323285. - DOI - PubMed
    1. Park HJ, Kusnadi A, Lee EJ, Kim WW, Cho BC et al. (2012) Tumor-infiltrating regulatory T cells delineated by upregulation of PD-1 and inhibitory receptors. Cell Immunol 278: 76-83. doi:10.1016/j.cellimm.2012.07.001. PubMed: 23121978. - DOI - PubMed
    1. Raimondi G, Shufesky WJ, Tokita D, Morelli AE, Thomson AW (2006) Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells. J Immunol 176: 2808-2816. PubMed: 16493037. - PubMed
    1. Keir ME, Butte MJ, Freeman GJ, Sharpe AH (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26: 677-704. doi:10.1146/annurev.immunol.26.021607.090331. PubMed: 18173375. - DOI - PMC - PubMed
    1. Dong H, Zhu G, Tamada K, Chen L (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 5: 1365-1369. doi:10.1038/70932. PubMed: 10581077. - DOI - PubMed

Publication types

MeSH terms