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
5107 - Tolerability of PCV in Low Grade Glioma: a Real World Experience
Presenter: Razia Aslam
Session: Poster Display session 1
Resources:
Abstract
6171 - Molecular EGFR/PD-L1 profile of glioblastoma: Hints for therapeutic strategies
Presenter: Wojciech Szopa
Session: Poster Display session 1
Resources:
Abstract
4418 - Role of Intraoperative MRI (iMRI) in neurosurgery, potential imaging tool for maximizing gross total resection (GTR) rate of CNS tumours.
Presenter: Shweta Wadhwa
Session: Poster Display session 1
Resources:
Abstract
4791 - Tumor related impairments of neurocognitive functions in patients with brain metastases
Presenter: Lei Wen
Session: Poster Display session 1
Resources:
Abstract
5372 - Is radiation therapy influencing Alzheimer’s in Brain and Head and Neck Cancers?
Presenter: Anas Saad
Session: Poster Display session 1
Resources:
Abstract
2329 - Mature Treatment Results of 120 Cases of Acoustic Neuroma Treated with Cyberknife at a single institution.
Presenter: Shawn Malone
Session: Poster Display session 1
Resources:
Abstract
3207 - A phase II/III trial of high-dose, intermittent sunitinib in patients with recurrent glioblastoma: the STELLAR study
Presenter: Cyrillo Brahm
Session: Poster Display session 1
Resources:
Abstract
3589 - CNS penetration and Preliminary Efficacy of Sacutizumab Govitecan in Breast Brain Metastasis and Glioblastoma: A Surgical Study
Presenter: Andrew Brenner
Session: Poster Display session 1
Resources:
Abstract
1969 - Wedge resection with omission of lymph node dissection as an optional treatment strategy in octogenarians or older with early stage non-small cell lung cancers
Presenter: Takahiro Mimae
Session: Poster Display session 1
Resources:
Abstract
5116 - Characterization of lung tumorspheres reveals cancer stem-like cells potential targets and prognostic markers in non-small cell lung cancer
Presenter: Alejandro Herreros Pomares
Session: Poster Display session 1
Resources:
Abstract