1969P - Intratumoral immune infiltrates in chondrosarcoma (ChS)

Background

Infiltrates of various immune cells play an important role in tumor(tu) microenvironment depending on cells' population. T lymphocytes (Tcells, CD3+) may stimulate or suppress immune response, depending on CD4 or CD8 phenotype, respectively. The other important group of cells are macrophages – anti-tumoral M1-like and pro-tumoral M2-like cells. Immunophenotype of ChS and characterization of immune markers involved in pathogenesis is still poorly understood. The aim of this study was characterization of immune cells infiltrates in ChS subtypes and correlate it with clinical outcomes.

Methods

We enrolled 113 patients(pts) diagnosed with primary ChS: 29 grade(G) 1, 41-G2, 25 -G3 and 18 dedifferentiated/mesenchymal cases. For immunohistochemical assessment tissue microarrays of central and peripheral region of the tu were prepared from formalin-fixed paraffin-embedded tissue blocks. IHC analysis covered CD3 (for T cells overall), CD8 (cytotoxic T cells), CD4 (helper T cells), CD68[PG-M1] (M1-like cells), CD68[KP1] and CD163 (M2-like cells), PD-1+ on lymphocytes, and PD-L1+ on tu cells. The number of positive stained cells per area (mm², quantitative methods) was defined. PD-L1 expression was evaluated as percent of positive cells. Correlations between expression of immune cells in central and peripheral regions of tu were assessed, and overall survival(OS) was analyzed.

Results

Median OS of all pts was 141 (95%CI: 37.8-) months. In central region of tu we identified significant positive correlation between presence of M1-like CD68+ and M2-like CD68+ macrophages (rho=0.69, p<0.001), as well as CD3 and CD4 cells (rho=0.72, p<0.001). The correlation of immune infiltrates presence between central and peripheral region of tu was low (rho ≤0.5). In multivariate Cox analysis presence of CD3 cells (HR 2.98, CI:1.43-6.23, p<0.01) and expression of PD-L1 (HR 1.01, CI:1.01-1.01, p<0.01) in central part of tu, as well as high grade of tu (G3/dedifferentiated/mesenchymal) predicted poorer survival. Other immune infiltrates were not significantly correlated with OS.

Conclusions

Beside high grade, PD-L1 expression and CD3 cell influx in central region of tu are independent poor prognostic factors in ChS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Maria Sklodowska-Curie National Research Institute of Oncology.

Funding

National Science Centre.

Disclosure

P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfizer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Member of Board of Directors, President: Polish Oncological Society. J. Blay: Financial Interests, Personal, Advisory Board: Bayer, Deciphera, GSK, Roche; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Invited Speaker: MSD, MSD; Financial Interests, Personal, Other, member of the supervisory board: Innate pharma; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. A.M. Czarnecka: Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre. All other authors have declared no conflicts of interest.