Biomarkers & Immunomonitoring in melanoma
Disease burden of melanoma
- Increase incidence
- Aggressive form of skin cancer
o Ability to metastasize
- 2020: 800 death (NL)
- Evolving therapeutic options since 2011
Melanoma
Prognostic / predictive biomarkers
- A prognostic biomarker provides information about the patients overall cancer outcome,
regardless of therapy, not specific patient but group of patients
- A predictive biomarker gives information about the effect of a therapeutic intervention,
predicts if somebody will react on therapy
Known prognostic clinical parameters (TNM, staging categories for cutaneous melanoma)
- Primary melanoma (Thichkness)
o Breslow thickness
o Ulceration
- Nodal metastases (Number)
o Number of lymph node metastases
o Size (microscopic or macroscopic)
- Distant metastases (site) (Metastases)
o Serum LDH level
o Prognose is more worse
Tumor:
CTLA-4: reduces in fase 1
PDA-1: plays role on place of tumor cells themselves (fase 7)
, Anti PD-1 mechanism:
- PD-L1 expression differs between patients
- (more) effect of PD-1 Ab if PD-L1 expression is present or high?
Tumor microenvironment:
Tumor infiltration:
1. T cell activation
2. T cell proliferation
3. Infiltration of tumor site
4. Tumor cell destruction
Tumor infiltrating lymphocytes (TIL)
- TIL as independent prognostic factor for lymph node metastases TIL might be prognostic for
survival
(A) 0: lymphocytes at the base of the melanoma, but they do not infiltrate the tumor
(B) 1: mild infiltrate of lymphocytes focally interspersed among the melanoma cells
(C) 2: dense multifocal infiltrate of lymphocytes interspersed among the melanoma cells
(D) 3: dense infiltrate of lymphocytes illustrated in the figure was present diffusely throughout
the tumor
Biomarkers in the tumor microenvironment
- H&E staining (tumor slides)
o Detectionj of lymphocytes
o Information about localization
- Flowcytometry (cell suspension)
o Presence and typing of cells
o No information about localization
- IHC (Immune histochemistry) (single stainings)
o Localization of cells
- mIHC (multiplex immune histochemistry)
o presence and localization of different cell types in one slide
o at BMS: Vectra mapping the T cell landscape near tumors
Automated quantitative pathology imaging system
Automated tissue segmentation: tumor vs normal tissue
Up to 8 fluorescent markers in 1 slide
Information about
Different cell types
localization, clusters, spread, in tumor, out tumor
Disease burden of melanoma
- Increase incidence
- Aggressive form of skin cancer
o Ability to metastasize
- 2020: 800 death (NL)
- Evolving therapeutic options since 2011
Melanoma
Prognostic / predictive biomarkers
- A prognostic biomarker provides information about the patients overall cancer outcome,
regardless of therapy, not specific patient but group of patients
- A predictive biomarker gives information about the effect of a therapeutic intervention,
predicts if somebody will react on therapy
Known prognostic clinical parameters (TNM, staging categories for cutaneous melanoma)
- Primary melanoma (Thichkness)
o Breslow thickness
o Ulceration
- Nodal metastases (Number)
o Number of lymph node metastases
o Size (microscopic or macroscopic)
- Distant metastases (site) (Metastases)
o Serum LDH level
o Prognose is more worse
Tumor:
CTLA-4: reduces in fase 1
PDA-1: plays role on place of tumor cells themselves (fase 7)
, Anti PD-1 mechanism:
- PD-L1 expression differs between patients
- (more) effect of PD-1 Ab if PD-L1 expression is present or high?
Tumor microenvironment:
Tumor infiltration:
1. T cell activation
2. T cell proliferation
3. Infiltration of tumor site
4. Tumor cell destruction
Tumor infiltrating lymphocytes (TIL)
- TIL as independent prognostic factor for lymph node metastases TIL might be prognostic for
survival
(A) 0: lymphocytes at the base of the melanoma, but they do not infiltrate the tumor
(B) 1: mild infiltrate of lymphocytes focally interspersed among the melanoma cells
(C) 2: dense multifocal infiltrate of lymphocytes interspersed among the melanoma cells
(D) 3: dense infiltrate of lymphocytes illustrated in the figure was present diffusely throughout
the tumor
Biomarkers in the tumor microenvironment
- H&E staining (tumor slides)
o Detectionj of lymphocytes
o Information about localization
- Flowcytometry (cell suspension)
o Presence and typing of cells
o No information about localization
- IHC (Immune histochemistry) (single stainings)
o Localization of cells
- mIHC (multiplex immune histochemistry)
o presence and localization of different cell types in one slide
o at BMS: Vectra mapping the T cell landscape near tumors
Automated quantitative pathology imaging system
Automated tissue segmentation: tumor vs normal tissue
Up to 8 fluorescent markers in 1 slide
Information about
Different cell types
localization, clusters, spread, in tumor, out tumor
