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
5011 - LCSCAF1 maintains cancer stem-like traits by stabilizing c-Myc protein and promotes metastasis and recurrence in lung cancer
Presenter: Tao Guo
Session: Poster Display session 1
Resources:
Abstract
4955 - XAF1 Enhances Temozolomide Induced Autophagic Cell Death through AMPK signaling pathway
Presenter: Mingoo Lee
Session: Poster Display session 1
Resources:
Abstract
5616 - The effect of cortisol on methylation patterns in breast cancer cell lines
Presenter: Haya Intabli
Session: Poster Display session 1
Resources:
Abstract
4649 - Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a Mediterranean population
Presenter: Judith Begona Ramirez Sabio
Session: Poster Display session 1
Resources:
Abstract
4984 - Whole transcriptomics analyses of mimicking Circulating Tumor Cells (CTCs) by single-cell RNA sequencing (scRNAseq)
Presenter: Jessica Garcia
Session: Poster Display session 1
Resources:
Abstract
5926 - Comparison of enzymatic- and bisulfite conversion to map the plasma cell-free methylome in cancer
Presenter: Nicole Lambert
Session: Poster Display session 1
Resources:
Abstract
5454 - Detection of low mutations in hepatocellular carcinoma by using circulating tumor DNA
Presenter: Esl Kim
Session: Poster Display session 1
Resources:
Abstract
4428 - Variants in the JAK1 and JAK2 genes in the risk and prognosis of patients with cutaneous melanoma
Presenter: Bruna Carvalho
Session: Poster Display session 1
Resources:
Abstract
4409 - P-Rex1 expression in breast cancer patients.
Presenter: Angela Lara Montero
Session: Poster Display session 1
Resources:
Abstract
4185 - Modulation of Risk of Cutaneous Melanoma Patients by Variants in STAT3 Gene and Functional Analysis
Presenter: Gabriela Gomez
Session: Poster Display session 1
Resources:
Abstract