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
2490 - Gender effect on the pharmacokinetics (PK) and pharmacodynamics (PD) of anamorelin (ANAM) in healthy volunteers and cancer patients with cachexia
Presenter: Stein Kaasa
Session: Poster Display session 1
Resources:
Abstract
4294 - The Patient Voice: An Irish Survey of Nutrition Attitudes & Access to Dietetic Care Throughout the Cancer Journey
Presenter: Erin Stella Sullivan
Session: Poster Display session 1
Resources:
Abstract
1925 - Homcology: home chemotherapy delivery in a simultaneous care project for frail advanced cancer patients
Presenter: Claudio Chini
Session: Poster Display session 1
Resources:
Abstract
4701 - Treatment-related adverse events and tolerability in patients with advanced non-squamous non-small cell lung cancer treated with first-line checkpoint inhibitors in combination with chemotherapy
Presenter: Ruth D'cunha
Session: Poster Display session 1
Resources:
Abstract
2985 - Clinical utility of a systematic toxicity assessment form (STAF) in patients with breast cancer receiving adjuvant or neoadjuvant therapy.
Presenter: Jwa Hoon Kim
Session: Poster Display session 1
Resources:
Abstract
2358 - Physicians’ satisfaction with Health-related quality of life (HRQoL) assessment in daily clinical practice using electronic patient-reported outcome (ePRO) for cancer patients.
Presenter: Guillaume Mouillet
Session: Poster Display session 1
Resources:
Abstract
5172 - Predictors of Survival in Patients with Incurable Cancer
Presenter: Erin Stella Sullivan
Session: Poster Display session 1
Resources:
Abstract
2281 - Patients and Physicians' Satisfaction with Telemedicine (TM) in Cancer Care and Factors that Correlate with a Positive Patient’s Experience
Presenter: Hurria Gondal
Session: Poster Display session 1
Resources:
Abstract
2193 - Adherence to ESMO 2014 guidelines on bone-targeting agent (BTA) initiation for breast and prostate cancer patients: real-world insights from practicing European physicians
Presenter: Alex Rider
Session: Poster Display session 1
Resources:
Abstract
2200 - Use of skeletal-related events preventive agents in patients with solid tumours and bone metastases in central Denmark
Presenter: Anders Boysen
Session: Poster Display session 1
Resources:
Abstract