Related Experiment Video

Updated: Dec 28, 2025

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
10:03

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes

Published on: November 11, 2016

10.2K

Stroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma

Elena Galvani1, Piyushkumar A Mundra1, Sara Valpione1,2

  • 1Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Manchester, UK.

Nature Communications
|February 14, 2020
PubMed

Insights

Immune checkpoint inhibitors (ICIs) show promise in melanoma treatment. This study identifies early biological markers of durable response to PD-1 blockade, aiding patient stratification for better outcomes.

Area of Science:

  • Oncology
  • Immunotherapy
  • Melanoma Research

Background:

  • Immune checkpoint inhibitors (ICIs) have revolutionized melanoma treatment.
  • However, the biological characteristics of durable responses to ICIs remain poorly understood.

Purpose of the Study:

  • To investigate the genetic and phenotypic changes associated with durable responses to programmed cell death-1 (PD-1) blockade in melanoma.
  • To identify early indicators of treatment response for improved patient stratification.

Main Methods:

  • Utilized a genetically engineered mouse model of oncogenic BRAF-driven melanoma.
  • Analyzed tumor samples from a mouse model and two independent early on-treatment anti-PD-1 melanoma patient cohorts.

Main Results:

  • Anti-PD-1 treatment resulted in responses in ~35% of tumors and prolonged survival in ~27% of animals in the mouse model.
  • Key features associated with prolonged response included increased stroma remodeling and reduced expression of proliferation markers.
  • These findings were validated in human patient cohorts.

Conclusions:

  • Identified specific biological features (stroma remodeling, reduced proliferation) linked to durable responses to PD-1 blockade in melanoma.
  • These insights offer a strategy for early identification of durable responders and improved patient stratification for ICI therapy.

More Related Videos

Author Spotlight: Recreating Melanoma Complexity with Patient-Derived Organoids for Immunotherapy Evaluation05:33

Author Spotlight: Recreating Melanoma Complexity with Patient-Derived Organoids for Immunotherapy Evaluation

Published on: September 6, 2024

2.2K
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells09:32

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells

Published on: February 8, 2018

15.3K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.8K
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.2K
Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
8.2K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.1K