Discovering dominant tumor immune archetypes in a pan-cancer census

Alexis J Combes; Bushra Samad; Jessica Tsui; Nayvin W Chew; Peter Yan; Gabriella C Reeder; Divyashree Kushnoor; Alan Shen; Brittany Davidson; Andrea J Barczak; Michael Adkisson; Austin Edwards; Mohammad Naser; Kevin C Barry; Tristan Courau; Taymour Hammoudi; Rafael J Argüello; Arjun Arkal Rao; Adam B Olshen; Immunoprofiler Consortium; Cathy Cai; Jenny Zhan; Katelyn C Davis; Robin K Kelley; Jocelyn S Chapman; Chloe E Atreya; Amar Patel; Adil I Daud; Patrick Ha; Aaron A Diaz; Johannes R Kratz; Eric A Collisson; Gabriela K Fragiadakis; David J Erle; Alexandre Boissonnas; Saurabh Asthana; Vincent Chan; Matthew F Krummel

doi:10.1016/j.cell.2021.12.004

Discovering dominant tumor immune archetypes in a pan-cancer census

Cell. 2022 Jan 6;185(1):184-203.e19. doi: 10.1016/j.cell.2021.12.004. Epub 2021 Dec 27.

Authors

Alexis J Combes¹, Bushra Samad², Jessica Tsui², Nayvin W Chew², Peter Yan², Gabriella C Reeder², Divyashree Kushnoor², Alan Shen², Brittany Davidson³, Andrea J Barczak⁴, Michael Adkisson⁴, Austin Edwards², Mohammad Naser², Kevin C Barry⁵, Tristan Courau², Taymour Hammoudi², Rafael J Argüello⁶, Arjun Arkal Rao², Adam B Olshen⁷; Immunoprofiler Consortium; Cathy Cai², Jenny Zhan², Katelyn C Davis², Robin K Kelley⁸, Jocelyn S Chapman⁹, Chloe E Atreya¹⁰, Amar Patel¹¹, Adil I Daud¹², Patrick Ha¹³, Aaron A Diaz¹⁴, Johannes R Kratz¹⁵, Eric A Collisson¹⁰, Gabriela K Fragiadakis¹⁶, David J Erle¹⁷, Alexandre Boissonnas¹⁸, Saurabh Asthana¹⁹, Vincent Chan²⁰, Matthew F Krummel²¹

Collaborators

Immunoprofiler Consortium:
Matthew Spitzer, Lawrence Fong, Amanda Nelson, Raj Kumar, Justin Lee, Arun Burra, Joy Hsu, Caroline Hackett, Karen Tolentino, Jasmine Sjarif, Peter Johnson, Evans Shao, Darrell Abrau, Leonard Lupin, Cole Shaw, Zachary Collins, Tasha Lea, Carlos Corvera, Eric Nakakura, Julia Carnevale, Michael Alvarado, Kimberley Loo, Lawrence Chen, Melissa Chow, Jennifer Grandis, Will Ryan, Ivan El-Sayed, David Jablons, Gavitt Woodard, Maxwell W Meng, Sima P Porten, Hideho Okada, Margaret Tempero, Andrew Ko, Kim Kirkwood, Scott Vandenberg, Denise Guevarra, Erica Oropeza, Chris Cyr, Pat Glenn, Jennifer Bolen, Amanda Morton, Walter Eckalbar

Affiliations

¹ Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: alexis.combes@ucsf.edu.
² Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
³ ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
⁴ UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
⁵ Translational Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁶ Aix Marseille University, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
⁷ UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94143, USA.
⁸ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
⁹ UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Departments of Obstetrics, Gynecology, and Reproductive Sciences, Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁰ UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
¹¹ UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
¹² Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
¹³ Department of Otolaryngology, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁴ Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁵ ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁶ ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine Division of Rheumatology, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁷ ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; Lung Biology Center, Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁸ Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses-CIMI, Paris, France.
¹⁹ UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94143, USA.
²⁰ ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
²¹ Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: matthew.krummel@ucsf.edu.

Abstract

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here "archetypes"-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy.

Keywords: Pan Cancer analysis; immune profiling; solid tumor microenvironement; system immunology; tumor immunology; unsupervised clustering.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor
Censuses*
Cluster Analysis
Cohort Studies
Computational Biology / methods
Flow Cytometry / methods
Gene Expression Regulation, Neoplastic
Humans
Neoplasms / classification
Neoplasms / genetics*
Neoplasms / immunology*
Neoplasms / pathology
RNA-Seq / methods
San Francisco
Transcriptome / genetics*
Tumor Microenvironment / immunology*
Universities

Substances

Biomarkers, Tumor

Abstract

Publication types

MeSH terms

Substances

Grants and funding