Evidence map›Paper›PMID 42342704›Full record

ArticleNature communications2026

Multimodal blood based proteomic profiling reveals insights into mechanisms of immunotherapy resistance.

Samuel J Wright, Izabella Zamora, Milan Parikh, Deepika Yeramosu, Marijana Rucevic, Moshe Sade-Feldman, Thomas J LaSalle, Emily M Blaum, Baolin Liu, Lynn Bi and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

34 authors.

Samuel J WrightBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Izabella ZamoraBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Milan ParikhBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1336-7883
Deepika YeramosuBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Marijana RucevicOlink Proteomics, Watertown, MA, USA.
Moshe Sade-FeldmanBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0022-0287
Thomas J LaSalleBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8390-6072
Emily M BlaumBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8656-8216
Baolin LiuBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Lynn BiBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Sarah KangBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Steven M BlumBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Ngan NguyenTeiko.bio, Salt Lake City, UT, USA.
Jamey GuessOlink Proteomics, Watertown, MA, USA.
Amrita KarOlink Proteomics, Watertown, MA, USA.
Alexis M SchneiderUniversity of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2158-6915
David LiebBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Elliot WoodsBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
William MichaudKrantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3664-2094
Aleigha R LawlessMass General Brigham Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0009-0009-3861-3164
Tatyana SharovaKrantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Sonia CohenKrantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Gyulnara KasumovaKrantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Michelle S KimKrantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Li-Chun ChengTeiko.bio, Salt Lake City, UT, USA.
Alexandra-Chloé VillaniBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7461-0408
Ryan J ParkMD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4725-2937
Russell W JenkinsBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6110-2148
Samuel J KlempnerHarvard Medical School, Boston, MA, USA.
Ryan J SullivanHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5344-6645
Keith T FlahertyHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3402-0478
Nir HacohenBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. nhacohen@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-2349-2656
Arnav MehtaBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. amehta@broadinstitute.org.ORCID http://orcid.org/0000-0002-0313-2848
Genevieve M BolandKrantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. gmboland@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-7522-6173

Funding

Dana Farber/Harvard Cancer Consortium Career Development Program in Clinical OncologyK12CA087723 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Tsai Ting · 2002 to 2026
$17.9M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
NCI NIH HHS K12 CA087723NIGMS NIH HHS T32 GM144273
6 · The paper itself

Abstract

Many cancer patients treated with immune checkpoint blockade (ICB) do not have durable treatment responses. Circulating biomarkers have the potential to identify patients with primary resistance or early progression on therapy to alter treatment course and potentially avoid unnecessary toxicity. Unbiased multimodal proteomic profiling in blood has been underexplored due to the previously limited scalability of multiplexing technologies or cohorts lacking time-series sampling. To address this, we performed plasma proteomic profiling of >2900 proteins and high-dimensional mass cytometry of peripheral blood lymphocytes across serial time points in 250 metastatic melanoma patients on ICB treatment. We further obtained 92 patient-matched tumor samples, which were processed for single-cell and/or bulk RNA sequencing. Proteins upregulated post-ICB were associated with inflammatory pathways involving the activation of effector immune functions. Expression of genes corresponding to these proteins was higher in immune cells involved in recruitment and tumor reactivity. Expression of genes corresponding to plasma proteins more abundant in non-responders was highest in suppressive myeloid subsets and malignant cells. We further posit the involvement of these non-responder genes in immunosuppressive and pro-tumor interactions, which we confirm using publicly available spatial transcriptomic data. We also find that epithelial-specific proteins in the circulation of responders post-ICB associate with patient toxicity and likely originate from degradation of healthy tissues. Together, these data represent extensive potential peripheral biomarker characterization using paired blood and tumor samples in melanoma patients treated with ICB, and begin to elucidate the complex interplay between tumors and the systemic immune response within the host.

Indexed as

Drug Resistance, NeoplasmImmune Checkpoint InhibitorsImmunotherapyMelanomaProteomicsBiomarkers, TumorBlood ProteinsGene Expression Regulation, NeoplasticHumansLymphocytesBiomarkers, TumorBlood ProteinsImmune Checkpoint Inhibitors

Identifiers

PMID42342704
PMCPMC13448642

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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.