1399PD - PD1 and PDL1 expression, tumoral microenvironment (TME) characterization and clinical implication in localized osteosarcoma

Date 10 October 2016
Event ESMO 2016 Congress
Session Sarcoma
Topics Bone Sarcomas
Presenter Emanuela Palmerini
Citation Annals of Oncology (2016) 27 (6): 483-492. 10.1093/annonc/mdw388
Authors E. Palmerini1, C. Agostinelli2, P. Picci3, S. Pileri4, P. Lollini5, K. Scotlandi1, M.S. Benassi1, S. Ferrari1
  • 1Muscoloskeletal Oncology, Istituto Ortopedico Rizzoli, 40136 - Bologna/IT
  • 2Hematology, Policlinico S. Orsola-Malpighi, Bologna/IT
  • 3Muscoloskeletal Oncology, Istituto Ortopedico Rizzoli, Bologna/IT
  • 4Haematopathology Unit, Bologna University School of Medicine, Bologna/IT
  • 5Cancerology, Policlinico S.Orsola-Malpighi-"Giorgio Prodi" - C.I.R.C., Bologna/IT

Abstract

Background

PD1/PDL1 immune checkpoint blockade provides clinical benefits in a variety of solid tumors. Scarce are data on PD1/PDL1 pathway and immunological infiltrates in osteosarcoma. We hypothesized that immune infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMA) to test this hypothesis.

Methods

Biopsies from 129 pts, prospectively treated from 04/2001 to 11/2006 (protocol ISG-OS1), were analyzed. TMA from representative areas were assembled. Clinical and pathological characteristics at diagnosis, immunological characterization (CD8, CD4, CD3, FOXP3, CD20, CD68) of TME, PD-1 expression on TME, and PD-L1 both on tumor (t) cells and TME were correlated with pts outcome.

Results

86/129 pts had adequate staining for all markers. Median age: 16 (range 4-39); high LDH: 36/86; high alkaline phosphatase (AP): 18/86. All pts underwent neoadjuvant chemotherapy and surgery. A good pathologic response (≥90% necrosis) was achieved by 45/86 pts. The IHC results are reported in the table.

PDL1(t) PD1(TME) PDL1(TME) CD8 CD3 FOXP3 CD20 CD68
Pos 0 19 12 74 77 28 25 85
Neg 86 67 74 12 9 56 61 1
With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-yr OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-yr OS for: a) good responders (good 89% vs poor 57%, p = 0.0001); b) pts with CD8 tumoral infiltrates (CD8+ 78% vs CD8- 50%, p = 0.003); c) pts with normal AP (AP normal 85% vs AP high 44%, p = 0.04). A non-significant inferior 5-yr OS was found in PDL1 (TME) positive cases (PDL1+ 58% vs PDL1- 77%, p = 0.14). No statistically significant difference in 5-yr OS according to PD1, FOXP3, CD68, CD20, age, gender or LDH. After multivariate analysis, good histologic response (p = 0.002) and CD8 infiltration (p = 0.02) were independently correlated with better survival.

Conclusions

While this study confirms the importance of good pathologic response,our findings support the hypothesis that CD8+ T effector cells presence in TME at diagnosis confers superior survival for pts with localized osteosarcoma.

Clinical trial identification

Legal entity responsible for the study

Emanuela Palmerini

Funding

Bologna University

Disclosure

All authors have declared no conflicts of interest.