Evidence map›Paper›PMID 41373645›Full record

ArticleInternational journal of molecular sciences2025

IL-15 Complexes Combined with PD-1 Blockade Affect Immune Cell Distribution, Localization, and Immune Signatures in Regressing Versus Non-Regressing Metastatic Breast Tumors.

Josef W Goldufsky, Anjelica F Reyes, Allie A Heller, Malia E Leifheit, Maram N Albalawi, Noah T King, Timothy M Kuzel, Jeffrey R Schneider, Amanda L Marzo

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Josef W GoldufskyDepartment of Internal Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL 60612, USA.
Anjelica F ReyesDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USA.
Allie A HellerDepartment of Internal Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL 60612, USA.ORCID 0000-0001-8008-3982
Malia E LeifheitDepartment of Internal Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL 60612, USA.
Maram N AlbalawiDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USA.
Noah T KingDepartment of Internal Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL 60612, USA.ORCID 0009-0008-0470-2380
Timothy M KuzelDepartment of Internal Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL 60612, USA.
Jeffrey R SchneiderDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USA.ORCID 0000-0001-9091-7653
Amanda L MarzoDepartment of Internal Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL 60612, USA.ORCID 0000-0002-5839-0430

Funding

American Association for Immunology Career Award 18060805Cohn Fellowship (Rush University) 23090803NIH HHS R21 AI121774-01A1Walder Foundation Innovation Top Up Award 22-0803
6 · The paper itself

Abstract

Rapid advancements in understanding how the immune system can eliminate tumors have quickly translated into breakthroughs in developing cancer therapeutics. Immune checkpoint inhibitors (ICIs) have shown great promise in several cancers; however, resistance can affect up to two-thirds of patients receiving ICIs. A significant limitation of the effectiveness of anti-PD-1 therapy centers around the insufficient levels of immune cells needed to recognize and kill cancer cells compared to the number of suppressive immune cells within the tumor microenvironment. Determining what is required to overcome the resistance to anti-PD-1 therapy in breast cancer remains a critical need. Our data demonstrate that IL-15 complexes injected intratumorally in combination with PD-1 blockade therapy induce regression of established luminal B mammary breast tumors. We show that IL-15 alone or in combination with anti-PD-1 drives changes in gene expression of pathways associated with TCR and co-stimulatory signaling, immune cell adhesion, and migration. Furthermore, we show that intratumoral injection of IL-15 complexes traffics to the tumor-draining lymph node, as evidenced by Light sheet microscopy, and colocalizes with the anti-PD-1 monoclonal antibody. We also identify the immune signatures, localization, and distribution of immune cells in regressing and non-regressing breast tumors.

Indexed as

Breast NeoplasmsImmune Checkpoint InhibitorsInterleukin-15Programmed Cell Death 1 ReceptorAnimalsCell Line, TumorFemaleHumansMiceTumor MicroenvironmentImmune Checkpoint InhibitorsInterleukin-15Programmed Cell Death 1 Receptoranti-PD-1breast cancerIL-15 complexesimmunofluorescenceintratumoralmetabolic pathways

Identifiers

PMID41373645
PMCPMC12692021

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.