A Pan-cancer Landscape of Interactions between Solid Tumors and Infiltrating Immune Cell Populations

April 30, 2025

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Publicated to: Clinical Cancer Research. 24 (15): 3717-3728 - 2018-08-01 24(15), DOI: 10.1158/1078-0432.CCR-17-3509

Authors:

Tamborero, David; Rubio-Perez, Carlota; Muinos, Ferran; Sabarinathan, Radhakrishnan; Piulats, Josep M; Muntasell, Aura; Dienstmann, Rodrigo; Lopez-Bigas, Nuria; Gonzalez-Perez, Abel

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Affiliations

Barcelona Inst Sci & Technol, Inst Res Biomed, Barcelona 08028, Spain - Author

Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain - Author

CIBERONC, Dept Med Oncol, Inst Catala Oncol IDIBELL, Barcelona, Spain - Author

Hosp del Mar, Res Inst, Barcelona, Spain - Author

Sage Bionetworks, Seattle, WA USA - Author

Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona 08002, Spain - Author

Vali dHebron Inst Oncol, Barcelona, Spain - Author

Abstract

Purpose: Throughout their development, tumors are challenged by the immune system, and they acquire features to evade its surveillance. A systematic view of these traits, which shed light on how tumors respond to immunotherapies, is still lacking. Experimental Design: Here, we computed the relative abundance of an array of immune cell populations to measure the immune infiltration pattern of 9,174 tumors of 29 solid cancers. We then clustered tumors with similar infiltration pattern to define immunophenotypes. Finally, we identified genomic and transcriptomic traits associated to these immunophenotypes across cancer types. Results: In highly cytotoxic immunophenotypes, we found tumors with low clonal heterogeneity enriched for alterations of genes involved in epigenetic regulation, ubiquitin-mediated proteolysis, antigen presentation, and cell-cell communication, which may drive resistance in combination with the ectopic expression of negative immune checkpoints. Tumors with immunophenotypes of intermediate cytotoxicity are characterized by an upregulation of processes involved in neighboring tissue invasion and remodeling that may foster the recruitment of immunosuppressive cells. Tumors with poorly cytotoxic immunophenotype tend to be of more advanced stages and bear a greater burden of copy number alterations and frequent alterations of cell cycle, hedgehog, beta-catenin, and TGF-beta pathways, which may cause immune depletion. Conclusions: We provide a comprehensive landscape of the characteristics of solid tumors that may influence (or be influenced by) the characteristics of their immune infiltrate. These results may help interpret the response of solid tumors to immunotherapies and guide the development of novel drug combination strategies. (C) 2018 AACR.

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Keywords

Acquired-resistanceBlockadeCd8-positive t-lymphocytesDna copy number variationsEpigenesis, geneticEvasionGene expression regulation, neoplasticGenomicsHumansImmunophenotypingImmunotherapyLymphocytes, tumor-infiltratingMetastatic melanomaMicroenvironmentNeoplasmsResponsesReveaTgf-betaTherapyTranscriptome

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Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal CLINICAL CANCER RESEARCH due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2018, it was in position 16/230, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 7.32. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-04, the following number of citations:

WoS: 235
Europe PMC: 210

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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United States of America.

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Awards linked to the item

D. Tamborero is supported by project SAF2015-74072-JIN, which is funded by the Agencia Estatal de Investigacion (AEI) and Fondo Europeo de Desarrollo Regional (FEDER). C. Rubio-Perez is supported by an FPI fellowship (BES-2013-063354) from the Spanish Ministry of Economy and Competitiveness. N. Lopez-Bigas acknowledges funding from the European Research Council (consolidator grant 682398). A. Gonzalez-Perez is supported by a Ramon y Cajal contract (RYC-2013-14554), which also covers the costs of this publication. The results shown here are in whole or part based upon data generated by the TCGA Research Network. Data generated by the Genotype-Tissue Expression (GTEx) Project, supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS, were also used. We thank Elena Gros (PhD) and Ignacio Melero (MD, PhD) for the scientific review and helpful discussions of the study, Fiorella Ruiz for the annotation of the TCGA clinical data, and Dvir Aran (PhD) for the support in the expression adjustment methodology. We also thank Eliezer Van Allen (MD, PhD) for providing the transcriptomic data of melanoma patients treated with anti-CTLA4 therapy.

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