Related Experiment Video

Updated: Jan 29, 2026

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
10:13

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

Published on: May 6, 2019

9.5K

A non-functional neoepitope specific CD8+ T-cell response induced by tumor derived antigen exposure in vivo

Mathias Vormehr1,2, Katharina Reinhard1, Renata Blatnik3

  • 1Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz, Germany.

Oncoimmunology
|February 7, 2019
PubMed

Insights

Cancer mutations can create neoepitopes that prime T-cell immunity. However, even dominant neoepitope-specific T cells may not effectively target tumors or mediate anti-cancer activity.

Area of Science:

  • Immunology
  • Cancer Research
  • Molecular Biology

Background:

  • Cancer mutations can serve as neoepitopes, eliciting T-cell responses crucial for anti-cancer immunity and immune checkpoint blockade (ICB).
  • Therapies aiming to broaden tumor-specific T-cell responses are of significant interest due to the limited spontaneous induction of mutation-specific T cells.

Purpose of the Study:

  • To investigate neoepitope-specific CD8+ T-cell responses in mice with CT26 colon carcinoma tumors.
  • To evaluate the functional relevance of T-cell responses against a specific neoepitope after various immunotherapy regimens.

Main Methods:

  • Screening of 2474 peptides covering 628 CT26 point mutations for immune reactivity.
  • Analysis of CD8+ T-cell responses induced spontaneously or post-immunotherapy.
  • Assessment of T-cell receptor (TCR) recognition and tumor cell lysis.
  • Evaluation of anti-tumoral activity following vaccination with a specific neoepitope.

Main Results:

  • All tested immunotherapies induced a significant CD8+ T-cell response against the Smc3 D733A neoepitope.
  • Despite being the immune-dominant neoepitope, Smc3 D733A-specific T cells and their TCRs could not recognize or lyse CT26 tumor cells.
  • Vaccination with the D733A neoepitope failed to induce anti-tumoral activity, even with specific T-cell induction.

Conclusions:

  • The study reports the first instance of neoepitope-specific CD8+ T cells, primed by tumor antigen exposure in vivo, being functionally irrelevant.
  • This finding highlights a critical disconnect between neoepitope recognition and effective anti-tumor immunity, challenging assumptions in cancer immunotherapy.
Keywords:
CD8+ T cell cytotoxicityCD8+ T cellsNeoepitopesT cell primingcancer immunotherapy

More Related Videos

A Three-dimensional Thymic Culture System to Generate Murine Induced Pluripotent Stem Cell-derived Tumor Antigen-specific Thymic Emigrants10:44

A Three-dimensional Thymic Culture System to Generate Murine Induced Pluripotent Stem Cell-derived Tumor Antigen-specific Thymic Emigrants

Published on: August 9, 2019

7.6K
Using Human Induced Pluripotent Stem Cells for the Generation of Tumor Antigen-specific T Cells10:57

Using Human Induced Pluripotent Stem Cells for the Generation of Tumor Antigen-specific T Cells

Published on: October 24, 2019

10.9K

Related Concept Videos

The Derivative as a Function01:26

The Derivative as a Function

A derivative quantifies how a function changes in response to variations in its input. It provides a localized rate of change, representing the slope of the tangent line to the function at any given point. When this process is applied systematically across the entire domain of the function, it yields a new function—the derivative function—which encodes the rate of change at every point. This concept is central to calculus and essential for understanding the behavior of dynamic...
82
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.5K
Derivatives of the Trigonometric Functions01:26

Derivatives of the Trigonometric Functions

The motion of a Ferris wheel rotating at a constant speed provides an intuitive model for understanding trigonometric functions and their derivatives. As a rider moves along the circular path, the vertical height above the ground changes smoothly and periodically over time. This vertical motion can be accurately represented by a sine function, reflecting the repeating pattern of ascent and descent inherent to circular motion.Height and Rate of ChangeIf the rider’s height is modeled by a...
450
Derivatives of Logarithmic Functions01:22

Derivatives of Logarithmic Functions

Logarithmic and Exponential RelationshipA logarithmic function is the inverse of an exponential function. If y = logb x then, it can be rewritten as by = x. This relationship allows for implicit differentiation, making logarithmic functions useful in calculus. Logarithmic scales are widely used to represent data that span multiple orders of magnitude, such as earthquake magnitudes (Richter scale) and sound intensity (decibels).Differentiation of Logarithmic FunctionsTo differentiate y = logb x,...
76
Antigen Presenting Cells01:22

Antigen Presenting Cells

The immune system is a complex network of cells and molecules that protects the body from foreign invaders. T cells, a type of white blood cell, play a crucial role in this process. They recognize and attack foreign substances, such as pathogens, that enter the body.
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
3.2K
Derivatives of Simple Functions01:27

Derivatives of Simple Functions

Derivatives quantify the rate of change of a function and can be interpreted geometrically as the slope of a straight line or the slope of a tangent line to a curve at a given point. In the context of a roller coaster, the derivative of the function describing the track’s horizontal position provides a mathematical description of how steep the path is at any location along the ride.Constant and Linear PathsA horizontal segment of a roller coaster can be modeled by a constant function,...
139