WEEK 14 - Oncology and molecular pathology (G)

α-GalCer (alpha-galactosylceramide)

= A potent glycolipid isolated from a marine sponge that is presented by CD1d molecules and strongly activates Type 1 NKT cells, inducing anti-tumor immune responses

Adjuvant

 = A substance that acts as a "danger signal" to enhance the immune response to an antigen

• In vaccines, adjuvants are necessary to induce the maturation of dendritic cells for proper T cell activation

Adoptive Cell Therapy

= A form of immunotherapy where immune cells (typically T cells) are collected, modified or expanded ex vivo, and then infused back into the patient to fight cancer

• Examples include TIL, CAR-T, and TCR-T therapy

BiTEs (Bispecific T-cell Engagers)

= Artificial molecules that can be used to "arm" oncolytic viruses, designed to bind to both a T cell and a tumor cell simultaneously, thereby redirecting the T cell to kill the tumor cell

Butyrophilins (e.g., BTN3A1)

= Cell surface molecules that sense the intracellular accumulation of phosphoantigens

• High levels of phosphoantigens cause a conformational change in butyrophilins, which is then recognized by the Vγ9Vδ2 T-cell receptor, leading to T cell activation

CAR-T Therapy (Chimeric Antigen Receptor T-cell)

= A type of adoptive cell therapy where a patient's T cells are genetically engineered to express a CAR, an antibody-like receptor that recognizes a specific surface antigen on tumor cells, independent of MHC presentation

CD1d

= A non-classical MHC-like molecule that specializes in presenting glycolipid antigens to Natural Killer T (NKT) cells

Cross-presentation

= The process by which an antigen-presenting cell, primarily a dendritic cell, takes up, processes, and presents extracellular antigens on MHC class I molecules to activate naïve CD8+ T cells

• This is essential for generating a cytotoxic T cell response against tumors. 

C-type Lectin Receptors (CLR)

= A class of receptors expressed on dendritic cells that recognize specific glycan (sugar) structures

• They can be targeted by vaccines to enhance antigen uptake, processing, and cross-presentation

CTLA-4 (Cytotoxic T-Lymphocyte-Associated protein 4)

= An inhibitory immune checkpoint receptor on T cells that primarily regulates T cell activation during the initial priming phase in lymph nodes

• It is a key target for immune checkpoint blockade (e.g., ipilimumab)

Dendritic Cell (DC)

= A potent antigen-presenting cell that resides in tissues, captures antigens, migrates to lymph nodes, and presents them to naïve T cells to initiate an adaptive immune response

• They are central to the mechanism of cancer vaccines

Glioblastoma (GBM)

= A highly invasive and aggressive type of brain cancer characterized by a locally and systemically immunosuppressive microenvironment, posing significant challenges for immunotherapy

Immune Checkpoint Blockade (ICB)

= A type of cancer therapy that uses antibodies to block inhibitory checkpoint proteins (like CTLA-4 and PD-1) on immune cells, thereby "releasing the brakes" and allowing T cells to more effectively attack cancer cells

Immune-related Adverse Events (irAEs)

= Side effects that occur with immunotherapy, particularly checkpoint inhibitors, resulting from widespread immune activation that can affect healthy organs. 

• Examples include colitis, hepatitis, pneumonitis, and endocrinopathies

Immunoscore

= A diagnostic tool that quantifies the presence and location of T cells (in the tumor core and invasive margin) within the tumor microenvironment

• It serves as an indicator of tumor recurrence and survival

Imaging Mass Cytometry (IMC)

= A high-dimensional imaging technology that uses antibodies tagged with heavy metal isotopes to simultaneously visualize dozens of markers in a tissue section without spectral overlap, enabling detailed spatial analysis of the tumor microenvironment

Mass Cytometry (CyTOF)

= A technology that uses the principles of mass spectrometry to perform high-dimensional, single-cell analysis of proteins

• It is used for deep immunophenotyping of cells from blood or tissue.

MHC (Major Histocompatibility Complex)

 = A set of cell surface proteins essential for the adaptive immune system to recognize foreign molecules. MHC class I presents endogenous peptides to CD8+ T cells, while MHC class II presents exogenous peptides to CD4+ T cells

Myeloid-Derived Suppressor Cells (MDSC)

= A heterogeneous population of immature myeloid cells that accumulate in the tumor microenvironment and suppress T cell responses, contributing to immune evasion. 

Neoantigen

= A new antigen that arises from tumor-specific mutations and is not present in normal, healthy cells

• They are highly immunogenic because the immune system has not developed tolerance to them. 

NKT cells (Natural Killer T cells)

= A subset of unconventional T cells that share characteristics of both NK cells and T cells

• Type 1 iNKT cells recognize glycolipid antigens presented on CD1d and can regulate both Th1 and Th2 immune responses

Oncolytic Virus (OV)

= A virus that is engineered or naturally selected to preferentially infect and lyse cancer cells while sparing normal cells

• OVs can also trigger a potent anti-tumor immune response. 

PD-1 (Programmed cell death protein 1)

= An inhibitory immune checkpoint receptor expressed on activated T cells

• Its engagement with its ligand, PD-L1 (often found on tumor cells), leads to T cell exhaustion and suppression of the anti-tumor response in the effector phase

Phosphoantigens

= Small, phosphorylated molecules produced during metabolic processes (endogenous) or by microbes (exogenous) that accumulate in cancer cells

• They activate Vγ9Vδ2 T cells via butyrophilin molecules

TCR-T Therapy (T-cell Receptor T-cell)

= A type of adoptive cell therapy where a patient's T cells are genetically engineered to express a new TCR that recognizes a specific tumor antigen-derived peptide presented by an MHC molecule

TIL Therapy (Tumor Infiltrating Lymphocytes)

= An adoptive cell therapy involving the extraction of a patient's own T cells from their tumor, expanding them to massive numbers in vitro, and re-infusing them into the patient

Tumor-Associated Macrophages (TAM)

= Macrophages within the tumor microenvironment that are often polarized to an immunosuppressive (M2-like) phenotype, promoting tumor growth and inhibiting effector T cell function

Tumor Microenvironment (TME)

= The complex ecosystem surrounding a tumor, consisting of tumor cells, immune cells, fibroblasts, vasculature, and extracellular matrix. The TME is often highly immunosuppressive. 

Vγ9Vδ2 T cells

 = The dominant subset of γδ-T cells in human peripheral blood

• Activated by phosphoantigens and can exert direct tumor cell lysis, produce proinflammatory cytokines, and function as antigen-presenting cells