Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Small Cell Lung Carcinoma

Breast Neoplasms

Melanoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Carcinoma, Renal Cell

Carcinoma, Small Cell

Urinary Bladder Neoplasms

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Kidney Neoplasms

Kidney Diseases

Head and Neck Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Small Cell Lung Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Immune Checkpoint Inhibitors

Hormones

Cetuximab

Angiogenesis Inhibitors

Mitogens

MDSC quantification in Metastatic melanoma patients undergoing first/second-line treatment with BRAF and MEK inhibitors (BRAFi+MEKi) or immune checkpoint inhibitors (antagonists of PD-1 or CTL4, or both) (n=100);

MDSC quantification in Metastatic HR+(hormone receptor positive)/ HER2-(Human Epidermal growth factor Receptor-2 negative) breast cancer patients already treated with a combination of an hormonal agent and a CDK(Cyclin-dependent kinase)4/6 inhibitor and receiving chemotherapy (n=100);

MDSC quantification Advanced RCC patients receiving immune checkpoint inhibitors (antagonists of PD-1, PD-L1 or CTL4, or combinations) or anti-angiogenics alone or combined with immune checkpoint inhibitors; locally advanced/metastatic UC(Urothelial Carcinoma) patients receiving first-line chemotherapy, immune checkpoint inhibitors or combinations (n=100);

MDSC quantification in SCCHN or SCC(Small Cell Carcinoma) patients treated with first-line chemotherapy, cetuximab,immune checkpoint inhibitors or combinations (n=100).

MDSC quantification in NSCLC patients undergoing radical surgery for stage III cancer (n=100);patients with unresectable/metastatic NSCLC receiving first line treatment with chemotherapy, immune checkpoint inhibitors (antagonists of PD-1, PD-L1 or CTL4) or combinations (n=100).

Age and gender-matched healthy donors (n=400) will be enrolled in the study, to allow us investigating the same immunological parameters under physiological conditions and define normal values for the myeloid-related biomarkers here assessed.

Blood sample will be collected at baseline and during therapy, and, optionally, in case of disease progression (PD).

MDSC quantification

Licia Rivoltini

Paola Frati

Licia Rivoltini, MD

The Serpentine (Stratify cancER PatiENTs by ImmuNosupprEssion) project, represents the most consistent effort so far attempted to translate MDSC into clinical practise by producing an off-the-shelf compliant assay for quantifying these cells in peripheral blood.

The study will demonstrate that this assay helps personalizing cancer therapies by tailoring them to immune patient features. The project will also take advantage of innovative and high-throughput techniques to define additional MDSC related biomarkers and, most importantly, to identify novel drugs for Myeloid-derived Suppressor Cells (MDSC) blocking in predisposed patients. Finally,it will perform the first survey assessing the link between MDSC and "perceived social isolation", an emerging western social problem recently shown to cause myeloid cell dysfunction and immunosuppression though neuroendocrine circuits. Globally, the Serpentine proposal has the ambitious goal to translate into the clinical oncological practise the use of MDSC quantification as a tool for the systematic assessment of systemic immunosuppression, providing at the same time operational insights into the strategies to overcome this pillar mechanism of cancer progression.

Whole blood sample;if available, archival tumor biopsies: they will also be collected to perform the characterization of the immune infiltrate by immunohistochemistry (starting from CD8+(cytotoxic T lymphocytes)/CD163+ ratio) or by transcriptional profile, including IFN(Interferon) and adaptive immunity- related signatures.

Quantifying Systemic Immunosuppression to Personalize Cancer Therapy

Frequency, in terms of percentage and absolute count of the defined cell subsets in whole blood and stored PBMC

Myeloid Index Score (MIS)=0 vs MIS\>0 or higher values

Index score values on plasma cytokine concentration or MDSC-miRs

Transcriptional signatures identified on PBMC and sorted myeloid cells form whole blood

Transcriptional signatures identified on sorted myeloid cells form whole blood

Phospho-kinome signature as assessed by Cytof analysis in stored PBMC

The concentration of individual metabolites or cluster of metabolites implicated in amino acid and lipid metabolism

Socioeconomic and psychological (perceived social isolation) score, calculated through a dedicated questionnaire

Spots Global Cancer Trial Database for mdsc quantification