Abstract 1282
Background
In many solid tumors, the setting of an immunosuppressive environment regulated by macrophages and immune checkpoints (ICP) is often a bad prognosis factor. Thus, targeting this immune environment led to the developments of new immunotherapies that raised high hopes for the treatment of solid tumors. Immunotherapy for chondrosarcoma (CHS) is comparatively less advanced partly because the immune environment of these rare tumors remains sparsely explored. However with their high resistance to conventional therapies CHS are typically tumors for which immunotherapies could be a solution. To get an exhaustive cartography of CHS immune landscape, identify prognosis factors and therapeutic targets, we described the immune populations and immune checkpoints of conventional CHS (CCHS) and dedifferentiated CHS (DD CHS), one of the rarest and most aggressive subtype of CHS.
Methods
Immunohistochemical methods (IHC) were used to map the expression of immune cells markers (CD3, CD8, CD68, CD163) on a cohort of 27 CCHS and 49 DD CHS. RT-qPCR was used to screen the expression of a panel of ICP, for the most promising ones, their expression was confirmed by IHC. The impact of the density of Tumor Infiltrating Lymphocytes (TIL), Tumor Associated Macrophages (TAM) and ICP on clinical outcome were analyzed.
Results
TAM were the main immune population encountered in DD and CCHS. Immune infiltrate composition was correlated with DD CHS’ outcome: a high CD68+ TAM density was associated with the presence of metastases at diagnosis (p < 0, 05) and a high CD68+/CD8+ ratio was an independent bad prognosis factor (p < 0.01). PDL1 was expressed in 42.6% of DD CHS while it was absent in CCHS. Of all the ICP tested, CSF1R, B7H3, SIRPA, TIM3 and LAG3 were expressed at mRNA level in both CHS subtypes. The expression of CSF1R by TAM was confirmed by IHC in 62.9% of CCHS and in 89.7% of DD CHS.
Conclusions
By showing that CHS immune environment is mainly composed of macrophages expressing CSF1R and that a high CD68 intratumoral density is correlated with the presence of metastases at diagnosis; our data reinforce the hypothesis of an immunosuppressive environment of this tumor. Our results converge to indicate that an immunomodulation through macrophages could be a promising therapeutic approach for CHS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Liddy Shriver; University of Lyon Claude Bernard 1.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2728 - MicroRNA expression and DNA methylation profiles do not distinguish between primary and recurrent well-differentiated liposarcoma
Presenter: Melissa Vos
Session: Poster Display session 1
Resources:
Abstract
3197 - Genomic Alterations, Tumor Mutation Burden and Prognosis of Chinese Cardiac Sarcoma Patients
Presenter: Na Zhu
Session: Poster Display session 1
Resources:
Abstract
4214 - Evaluation of a peptide-conjugated alkylator melflufen in osteosarcoma preclinical models
Presenter: Konstantin Byrgazov
Session: Poster Display session 1
Resources:
Abstract
2654 - Expression analysis of NHEJ and HR genes in Ewing sarcomas: indications of DSB repair dysfunction
Presenter: Anastasios Kyriazoglou
Session: Poster Display session 1
Resources:
Abstract
4383 - Epidemiology of Synovial Sarcoma in EU28 countries
Presenter: Nedra Joseph
Session: Poster Display session 1
Resources:
Abstract
1937 - Resection Of High-Grade Large Soft Tissue Sarcoma With Adequate Wide Margin Can Lead To Good Local Control Without Adjuvant Radiotherapy
Presenter: Toshiyuki Kunisada
Session: Poster Display session 1
Resources:
Abstract
3757 - Influence of eribulin on proliferation, migration and invasion properties of leiomyosarcoma cell line models
Presenter: Marta Mendiola
Session: Poster Display session 1
Resources:
Abstract
1040 - EREMISS: Efficacy of regorafenib (REG) as maintenance therapy in non-adipocytic soft tissue sarcomas (STS) having received 1st-line doxorubicin-based chemotherapy (Doxo-CT)
Presenter: Nicolas Penel
Session: Poster Display session 1
Resources:
Abstract
1048 - A Phase 2 biomarker-driven study evaluating the clinical efficacy of an MDM2 inhibitor, milademetan, in patients with intimal sarcoma, a disease with a high unmet need
Presenter: Kan Yonemori
Session: Poster Display session 1
Resources:
Abstract
1511 - A pilot study of oral paclitaxel (ORAXOL) in subjects with cutaneous angiosarcomas (KX-ORAX-010)
Presenter: Herbert Loong
Session: Poster Display session 1
Resources:
Abstract