Cellular neighborhoods govern antitumor T-cell infiltration following anti-CTLA-4 in melanoma with primary resistance to anti-PD-1

In the phase 2 trial SWOG S1616 (NCT03033576), patients with advanced melanoma with primary resistance to anti-PD-1/L1 therapies had improved outcomes on the combination of the anti-CTLA-4 antibody ipilimumab with continued anti-PD-1 with nivolumab, over ipilimumab alone. Baseline biopsies from patients responsive to combination therapy had increased transcriptomic expression of complement by myeloid cells, interferon pathways by endothelial cells, and oxidative phosphorylation and lipid metabolism by melanoma cells. Using spatial proteomics, some on-therapy biopsies from patients responding to combination therapy had networks of activated CD8 T cells nearby melanoma cells, while others had T cells and myeloid cells, reflective of different timepoints in a dynamic antitumor response. Conversely, biopsies from patients progressing on combination immunotherapy displayed impaired T-cell infiltration adjacent to plasma cells. Our results define cellular neighborhoods and transcriptomes in melanoma biopsies when reversing resistance to anti-PD-1 with the addition of anti-CTLA4, and plasma cell sheets in non-responding biopsies.

Authors

Institutions

Publication Details

Journal
Cancer Discovery
Published
2026-04-21
DOI
https://doi.org/10.1158/2159-8290.cd-25-1745
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Cellular neighborhoods govern antitumor T-cell infiltration following anti-CTLA-4 in melanoma with primary resistance to anti-PD-1

Frances A. Collichio, Ivan Perez Garcilazo, Lacey Padrón, Adrienne I. Victor et al.
Cancer Discovery
Cancer Immunotherapy and Biomarkers
article

Cellular neighborhoods govern antitumor T-cell infiltration following anti-CTLA-4 in melanoma with primary resistance to anti-PD-1

Frances A. Collichio, Ivan Perez Garcilazo, Lacey Padrón, Adrienne I. Victor, Agustin Vega-Crespo, Sapna Pradyuman Patel, Ari M. Vanderwalde, Philip O. Scumpia, Jessica Maxey, Kari Kendra, Nataly Naser Al Deen, Lawrence F. Kuklinski, Katie Marie Campbell, Jia Ming Chen, Egmidio Medina, Silvia Boffo, Nikhil I. Khushalani, Daniel K. Wells, Siwen Hu‐Lieskovan, R. Schiemann, D CHEN, Jeffrey A. Sosman, Ignacio Baselga-Carretero, Antoni Ribas, Kim Margolin, Thach‐Giao Truong, Cynthia R. Gonzalez, Alexandra P. Ikeguchi, Alan E. Zelin, James Moon, Sai S. Chelluri, C Chang, Michael C. Wu, Sarah Samorodnitsky, Christine N. Spencer, Marshall A. Thompson, Shay Bellasea, Rangasamy Elumalai, Bartosz Chmielowski, Marc Visitacion, Zaid E. Bustami, Douglas B. Johnson
article en

Abstract

In the phase 2 trial SWOG S1616 (NCT03033576), patients with advanced melanoma with primary resistance to anti-PD-1/L1 therapies had improved outcomes on the combination of the anti-CTLA-4 antibody ipilimumab with continued anti-PD-1 with nivolumab, over ipilimumab alone. Baseline biopsies from patients responsive to combination therapy had increased transcriptomic expression of complement by myeloid cells, interferon pathways by endothelial cells, and oxidative phosphorylation and lipid metabolism by melanoma cells. Using spatial proteomics, some on-therapy biopsies from patients responding to combination therapy had networks of activated CD8 T cells nearby melanoma cells, while others had T cells and myeloid cells, reflective of different timepoints in a dynamic antitumor response. Conversely, biopsies from patients progressing on combination immunotherapy displayed impaired T-cell infiltration adjacent to plasma cells. Our results define cellular neighborhoods and transcriptomes in melanoma biopsies when reversing resistance to anti-PD-1 with the addition of anti-CTLA4, and plasma cell sheets in non-responding biopsies.

Cancer Discovery
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), University of North Carolina Health Care (US), The University of Texas MD Anderson Cancer Center (US), Agilent Technologies (United States) (US), University of California, Los Angeles (US), Moffitt Cancer Center (US), Fred Hutch Cancer Center (US), Saint John's Health Center (US), Parker Institute for Cancer Immunotherapy (US), Michigan Cancer Research Consortium (US), Kaiser Permanente Vallejo Medical Center (US), Bristol-Myers Squibb (Belgium) (BE), Caris Life Sciences (United States) (US), University of Utah Health Care (US), Cancer Research Foundation (US), Robert H. Lurie Comprehensive Cancer Center of Northwestern University, University of Colorado Anschutz Medical Campus (US), The Ohio State University (US), University of Rochester (US), Columbia University (US), Vanderbilt University Medical Center (US)
Good health and well-being
Openalex Percentile: Top 11%
Cancer Immunotherapy and Biomarkers
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.