Related Experiment Video

Updated: Nov 19, 2025

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
10:04

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells

Published on: August 1, 2025

1.1K

De-novo and acquired resistance to immune checkpoint targeting

Nicholas L Syn1, Michele W L Teng2, Tony S K Mok3

  • 1Department of Haematology-Oncology, National University Cancer Institute, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore.

The Lancet. Oncology
|December 7, 2017
PubMed

Insights

Immune checkpoint inhibitors show promise but many patients relapse. Understanding tumor mutations and developing combination therapies are key to overcoming resistance and restoring anti-tumor immunity.

Area of Science:

  • Immunology
  • Oncology
  • Genomics

Background:

  • Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 improve cancer treatment outcomes.
  • However, initial response rates are limited, and many patients eventually experience relapse due to acquired drug resistance.

Purpose of the Study:

  • To review the mechanisms of tumor immune evasion and resistance to ICIs.
  • To discuss strategies for overcoming immune refractoriness in cancer.

Main Methods:

  • Analysis of massively parallel sequencing data to identify tumor mutations associated with immune evasion.
  • Review of current literature on ICI resistance and combination therapies.

Main Results:

  • Acquired defects in interferon receptor signaling and antigen presentation are implicated in tumor cells evading T-cell-mediated immunosurveillance.
  • Cancer genomes exhibit signatures of clonal evolution and selection contributing to resistance.

Conclusions:

  • Understanding the genetic basis of immune resistance is crucial for developing effective cancer therapies.
  • Combination strategies are being developed to re-establish immunosurveillance in immune-refractory tumors.

More Related Videos

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function08:04

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

Published on: February 27, 2019

12.2K
Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.4K

Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
864
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.5K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
6.0K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.1K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.2K
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
929