Related Experiment Video

Updated: Feb 11, 2026

Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer
06:49

Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer

Published on: February 10, 2023

2.8K

Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer

Matthew D Hellmann1, Tavi Nathanson2, Hira Rizvi3

  • 1Department of Medicine, Memorial Sloan Kettering Cancer Center, 885 2(nd) Avenue, New York, NY 10017, USA; Weill Cornell School of Medicine, New York, NY, USA; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Cancer Cell
|April 17, 2018
PubMed

Insights

High tumor mutation burden (TMB) predicts better response to combination immunotherapy in non-small-cell lung cancer (NSCLC). Low TMB indicates poor response, even with combined PD-1 and CTLA-4 blockade.

Area of Science:

  • Oncology
  • Immunotherapy
  • Genomics

Background:

  • Combination immune checkpoint blockade shows promise in lung cancer.
  • Predictors for response to combination therapy remain unclear.

Purpose of the Study:

  • To identify predictors of response to combination immunotherapy in non-small-cell lung cancer (NSCLC).
  • To investigate the role of tumor mutation burden (TMB) in predicting efficacy of PD-1 plus CTLA-4 blockade.

Main Methods:

  • Whole-exome sequencing was used to analyze NSCLC tumors from patients treated with combination immunotherapy.
  • Multivariable analysis was performed to assess the association between TMB, PD-L1 expression, and treatment outcomes.

Main Results:

  • High tumor mutation burden (TMB) was associated with improved objective response, durable benefit, and progression-free survival.
  • TMB was an independent predictor of efficacy and the strongest feature in multivariable analysis.
  • Combination immunotherapy did not overcome the negative predictive impact of low TMB in NSCLC.

Conclusions:

  • Tumor mutation burden (TMB) is a significant predictor of response to combination immunotherapy in NSCLC.
  • TMB should be considered in future clinical trials evaluating PD-(L)1 and CTLA-4 blockade in NSCLC.
Keywords:
CTLA-4PD-1TMBimmunotherapylung cancermutation burden

More Related Videos

Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients07:43

Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients

Published on: September 25, 2018

11.1K
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing05:17

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

Published on: October 10, 2025

428

Related Concept Videos

Distinctive Features of Adult Stem Cells vs Cancer Stem Cells01:18

Distinctive Features of Adult Stem Cells vs Cancer Stem Cells

A stem cell is an unspecialized cell that can divide without limit as needed and can, under specific conditions, differentiate into specialized cells.
Adult stem cells
Adult stem cells are tissue-specific; hence, they divide to develop the tissue from which they originate. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of the skin. Adult bone marrow has three distinct types of stem cells:...
4.5K
Genomics02:02

Genomics

Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
40.9K
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.
2.0K
Lung Capacity01:47

Lung Capacity

The air in the lungs is measured in volumes and capacities. Lung volume measures reflect the amount of air taken in, released, or left over after a lung function, like a single inhalation. Lung capacity measures are sums of two or more lung volume measures.
56.4K
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
37.3K
Genome Size and the Evolution of New Genes03:21

Genome Size and the Evolution of New Genes

While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
9.2K