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
. 2015 Mar;46(3):357-65.
doi: 10.1016/j.humpath.2014.11.001. Epub 2014 Nov 15.

Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment

Sandra P D'Angelo  1 , Alexander N Shoushtari  2 , Narasimhan P Agaram  3 , Deborah Kuk  4 , Li-Xuan Qin  4 , Richard D Carvajal  5 , Mark A Dickson  6 , Mrinal Gounder  6 , Mary Louise Keohan  6 , Gary K Schwartz  7 , William D Tap  6
Affiliations

Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment

Sandra P D'Angelo et al. Hum Pathol. 2015 Mar.

Abstract

The prognostic and predictive implications of programmed death-ligand 1 (PD-L1) is unknown in sarcoma. We sought to examine the immune milieu in sarcoma specimens. We evaluated PD-L1 expression by immunohistochemistry in sarcoma specimens and quantified tumor-infiltrating lymphocytes (TIL). We correlated expression with clinical parameters and outcomes. Fifty sarcoma patients treated at Memorial Sloan Kettering Cancer Center were selected. Using the DAKO PD-L1 immunohistochemistry assay and archival formalin-fixed paraffin-embedded tissue specimens; PD-L1 expression was examined. Macrophage and lymphocyte PD-L1 status was determined qualitatively. TIL was quantified. Associations between PD-L1 expression in tumor, macrophages and lymphocytes, TIL and clinical-pathological characteristics were performed. The median age was 46 years (range, 22-76), and 66% of patients were men. Tumor, lymphocyte and macrophage PD-L1 expression was noted in 12%, 30% and 58%, respectively, with the highest prevalence in gastrointestinal stromal tumors (29%). Lymphocyte and macrophage infiltration was present in 98% and 90%, respectively. There was no association between clinical features, overall survival and PD-L1 expression in tumor or immune infiltrates. Lymphocyte and macrophage infiltration is common in sarcoma, but PD-L1 tumor expression is uncommon in sarcoma with the highest frequency observed in gastrointestinal stromal tumors. There was no association between PD-L1 expression, TIL and clinicopathological features and overall survival; however, this is limited by the heterogenous patient sample and minimal death events in the studied cohort.

Keywords: Immunotherapy; PD-1; PD-L1; Sarcoma; Tumor infiltrating lymphocyte CD3+, CD4+, CD8+, FOXP3+.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Percentages of respective TIL
This is the percentage of the respective lymphocyte subset (CD3+, CD4+, CD8+ and FOXP3+) of the total cells present.
Figure 2
Figure 2. Representative images of multiplex TIL staining
A representative 20× field of staining was spectrally imaged. CD3+ was stained in red chromogen in figures A,B,D,E and DAB chromogen in figures C and F. CD8+ was stained in DAB in figures B and E and in purple chromogen in figure F. PD-1 was stained in DAB in figures A and D. FOXP3+ was stained in red chromogen in figures C and F. A: CD3+PD-1 multiplex IHC in angiosarcoma patient. B: CD3+CD8+ multiplex IHC in angiosarcoma patient. C: CD3+CD4+FOXP3+ multiplex IHC in angiosarcoma patient. D: CD3+PD-1 multiplex IHC in GIST patient. E: CD3+CD8+ multiplex IHC in GIST patient. F: CD3+CD4+FOXP3+ multiplex IHC in GIST patient. Abbreviations: GIST- gastrointestinal stromal tumor
Figure 3
Figure 3. Representative images of positive PD-L1 staining by IHC in (A) Gastrointestinal stromal tumor and (B) Radiation-associated pleomorphic sarcoma, arrows indicate PD-L1 positive cells
A representative 20× field of staining was spectrally imaged. Negative PD-L1 staining in (C) Gastrointestinal stromal tumor and (D) synovial sarcoma. PD-L1 staining is indicated by red chromogen. Abbreviations: GIST- gastrointestinal stromal tumor, PNET peripheral nerve sheath tumor
See this image and copyright information in PMC

References

    1. Brennan MFAC, Maki RG. Management of Soft Tissue Sarcoma. New York: Springer; 2012.
    1. Rusakiewicz S, Semeraro M, Sarabi M, et al. Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors. Cancer Res. 2013;73:3499–3510. - PubMed
    1. Berghuis D, Santos SJ, Baelde HJ, et al. Pro-inflammatory chemokine-chemokine receptor interactions within the Ewing sarcoma microenvironment determine CD8(+) T-lymphocyte infiltration and affect tumour progression. J Pathol. 2011;223:347–357. - PubMed
    1. Sorbye SW, Kilvaer T, Valkov A, et al. Prognostic impact of lymphocytes in soft tissue sarcomas. PLoS One. 2011;6:e14611. - PMC - PubMed
    1. Zhang L, Zhao Y. The regulation of Foxp3 expression in regulatory CD4(+)CD25(+)T cells: multiple pathways on the road. J Cell Physiol. 2007;211:590–597. - PubMed

Publication types