Thesis Terms

Kynurenine

A metabolite derived from tryptophan that suppresses immune cell function in tumors.

Cancer

A disease characterized by uncontrolled cell growth and often associated with immune evasion.

Cell

A single unit of life; in this context, often refers to immune cells like T cells.

CAR (Chimeric Antigen Receptor)

A synthetic receptor engineered into T cells to recognize and attack cancer cells.

Tryptophan

An essential amino acid used in protein synthesis and metabolized into kynurenine in tumors.

Tumor

An abnormal mass of tissue resulting from uncontrolled cell division, often targeted in immunotherapy.

Promoter

A DNA sequence that initiates gene transcription, used in synthetic biology to control gene expression.

Expression

The process by which information from a gene is used to synthesize functional gene products like proteins.

KYNase (Kynureninase)

An enzyme that breaks down kynurenine, reducing its immunosuppressive effects.

Immune

Refers to the body’s defense system against disease, including cancer.

Signal

A molecular cue that triggers a cellular response, such as gene expression or immune activation.

TME (Tumor Microenvironment)

The environment around a tumor, including immune cells, blood vessels, and signaling molecules.

Secretion

The process by which cells release substances, such as enzymes or cytokines, into their surroundings.

Enzyme

A protein that catalyzes biochemical reactions, like breaking down metabolites in cancer therapy.

Cytotoxicity

The ability of certain cells, like T cells, to kill cancer cells.

Cytokines

Small proteins released by cells that affect the behavior of other cells, crucial in immune responses.

Metabolism

The set of life-sustaining chemical reactions in organisms, often altered in cancer cells.

Inducible

Capable of being activated under specific conditions, such as in response to kynurenine.

Receptor

A protein on the cell surface or inside a cell that binds to specific molecules and triggers a response. Promoters – DNA sequences that initiate transcription of a gene, often engineered for controlled gene expression.

Levels

Refers to the concentration or amount of a substance, such as kynurenine or tryptophan, in a biological system.

Low

Indicates reduced levels or concentrations, often used in the context of nutrient availability in tumors.

Secrete

The process by which cells release substances like enzymes or cytokines into the extracellular space.

Enzymes

Biological catalysts that speed up chemical reactions, such as breaking down immunosuppressive metabolites.

Cytokine

A type of signaling molecule used by immune cells to communicate and coordinate responses.

Metabolite

A small molecule involved in metabolism, such as kynurenine, which can influence immune function.

Indoleamine 2,3-dioxygenase (IDO)

An enzyme that converts tryptophan into kynurenine, contributing to immune suppression.

Tryptophan-kynurenine pathway

A metabolic route that degrades tryptophan into kynurenine, often hijacked by tumors.

AhR (Aryl hydrocarbon receptor)

A receptor that binds kynurenine and regulates gene expression, affecting immune responses.

Transduction

The process of introducing genetic material into cells, often used to engineer CAR T cells.

Luciferase

An enzyme used in bioluminescence assays to measure gene expression or cell activity.

Granzyme B

A protein released by cytotoxic T cells to induce apoptosis in target cells.

Perforin

A protein that forms pores in target cell membranes, aiding in the delivery of granzymes.

CD28

A co-stimulatory molecule on T cells that enhances activation and survival.

4-1BB

Another co-stimulatory molecule that promotes T cell proliferation and persistence.

CD3ζ (CD3 zeta)

A signaling component of the T cell receptor complex, essential for T cell activation.

MUC16

A tumor-associated antigen targeted by engineered CAR T cells in this research.

HEK293T

A human cell line commonly used in research for producing proteins and viral vectors.

Retrovirus

A type of virus used to deliver genetic material into cells for stable gene expression.

Fusion tag

A protein or peptide added to another protein to aid in purification, detection, or secretion.

Signal peptide

A short amino acid sequence that directs the transport of a protein to specific parts of the cell or for secretion.

Transfection

The process of introducing nucleic acids into cells to produce genetically modified cells.

Supernatant

The liquid above a solid residue after centrifugation, often containing secreted proteins.

Lysate

A fluid containing the contents of lysed cells, used to analyze intracellular proteins.

Absorbance

A measure of the amount of light absorbed by a solution, used in enzyme activity assays.

Plate reader

A laboratory instrument used to detect biological, chemical, or physical events in samples in microplates.

ELISA (Enzyme-Linked Immunosorbent Assay)

A test that uses antibodies and color change to identify a substance.

Cytomegalovirus (CMV) promoter

A strong viral promoter used to drive high levels of gene expression in mammalian cells.

Codon optimization

Modifying DNA sequences to improve protein expression in a specific organism.

Spinoculation

A method to enhance viral infection of cells by centrifugation.

Splenocytes

A mixture of immune cells isolated from the spleen, often used in immunological research.

Luciferin

A substrate used in bioluminescence assays that emits light when catalyzed by luciferase.

IV injection (Intravenous injection)

A method of delivering substances directly into a vein.

IL-2 (Interleukin-2)

A cytokine that promotes T cell proliferation and survival.

Checkpoint blockade

A cancer therapy that inhibits proteins like PD-1 to enhance immune responses.

PD-1 (Programmed cell death protein 1)

An immune checkpoint receptor that downregulates immune responses.

Rechallenge

Reintroducing cancer cells into a previously treated animal to test immune memory.

Immunological memory

The ability of the immune system to respond more rapidly and effectively to pathogens it has encountered before.

Pharmacokinetics (PK)

The study of how a drug is absorbed, distributed, metabolized, and excreted in the body.

Antibody

A protein produced by the immune system that binds to specific antigens to neutralize or mark them for destruction.

T cell receptor (TCR)

A molecule on T cells that recognizes antigens presented by other cells.

Antigen

A substance that induces an immune response, often a target for CAR T cells.

Apoptosis

Programmed cell death, a mechanism used by immune cells to eliminate cancer cells.

Transcription

The process of copying DNA into RNA, the first step in gene expression.

Translation

The process of synthesizing proteins from RNA templates.

Gene

A segment of DNA that encodes a functional product, usually a protein.

DNA (Deoxyribonucleic acid)

The molecule that carries genetic instructions in living organisms.

RNA (Ribonucleic acid)

A molecule involved in coding, decoding, regulation, and expression of genes.

GCN2 (General Control Nonderepressible 2)

A kinase that senses amino acid deprivation and inhibits protein synthesis.

eIF2α (Eukaryotic Initiation Factor 2 alpha)

A protein involved in initiating translation, regulated by GCN2.

ATF4 (Activating Transcription Factor 4)

A transcription factor activated during cellular stress responses.

WARS (Tryptophanyl-tRNA synthetase)

An enzyme that attaches tryptophan to its tRNA, aiding protein synthesis.

tRNA (Transfer RNA)

A type of RNA that brings amino acids to the ribosome during protein synthesis.

Amino acid

The building blocks of proteins, essential for cell function and growth.

T cell anergy

A state of T cell inactivity where the cell cannot respond to its antigen.

Proliferation

The process of cell multiplication or growth, important for immune responses.

Cytotoxic T cell

A type of T cell that kills cancer cells and virus-infected cells.

Helper T cell

A T cell that assists other immune cells by releasing cytokines.

Memory T cell

A T cell that remains in the body after an infection or treatment, ready to respond quickly if the antigen reappears.

Regulatory T cell (Treg)

A type of T cell that suppresses immune responses to maintain tolerance and prevent autoimmunity.

MHC (Major Histocompatibility Complex)

A set of proteins on cell surfaces that present antigens to T cells.

Antigen-presenting cell (APC)

A cell that displays antigens on its surface to activate T cells.

mTOR (Mechanistic Target of Rapamycin)

A protein that regulates cell growth, metabolism, and survival, important in T cell activation.

Th17 cell

A subset of helper T cells involved in inflammation and autoimmune responses.

FoxP3

A transcription factor critical for the development and function of regulatory T cells.

RORγt

A transcription factor important for the development of Th17 cells.

Chromatin accessibility

The openness of DNA to transcription machinery, influencing gene expression.

Positive feedback loop

A process where the output of a system enhances the original stimulus, such as kynurenine increasing IDO1 expression.

Synthetic promoter

An engineered DNA sequence designed to control gene expression in response to specific signals.

Minimal promoter

A basic promoter sequence that requires additional elements to drive strong gene expression.

Dioxin response element (DRE)

A DNA sequence that binds the AhR/ARNT complex to regulate gene expression.

FICZ (6-Formylindolo[3,2-b]carbazole)

A potent AhR agonist used to activate DRE-containing promoters.

Gaussia luciferase

A secreted luciferase enzyme used as a reporter in gene expression studies.

Flow cytometry (FACS)

A technique used to analyze the physical and chemical characteristics of cells.

Mean fluorescence intensity (MFI)

A measure of the average fluorescence signal from a population of cells.

Nanoluciferase

A small, bright luciferase enzyme used in bioluminescent imaging.

Furimazine

A substrate for nanoluciferase that produces light upon reaction.

IVIS imaging

A technique for visualizing bioluminescent or fluorescent signals in live animals.

Tumor-associated antigen

A protein or molecule expressed on cancer cells that can be targeted by immune therapies.

Immunotherapy

A treatment that uses the body’s immune system to fight diseases like cancer.

Adoptive cell therapy (ACT)

A type of immunotherapy where immune cells are collected, modified, and reinfused into the patient.