Evidence map›Paper›PMID 38443917›Full record

ArticleJournal of translational medicine2024

Comparing anti-tumor and anti-self immunity in a patient with melanoma receiving immune checkpoint blockade.

Shuming Chen, Tracee L McMiller, Abha Soni, Farah Succaria, John-William Sidhom, Laura C Cappelli, Livia A Casciola-Rosen, Isaac R Morales, Preethi Sankaran, Alan E Berger and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 9% of its field
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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. 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

18 authors at 2 institutions in 1 country.

Shuming ChenDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Tracee L McMillerDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Abha SoniDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Farah SuccariaDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
John-William SidhomDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Laura C CappelliDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Livia A Casciola-RosenDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Isaac R MoralesDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Preethi SankaranDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Alan E BergerDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Julie Stein DeutschDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Qingfeng C ZhuDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Robert A AndersDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Jody E HooperDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Drew M PardollDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Evan J LipsonDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Janis M TaubeDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Suzanne L TopalianDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. stopali1@jhmi.edu.ORCID 0000-0002-0821-8587
Bloomberg (United States) · USJohns Hopkins University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
PD-1/PD-L1 modulation in cancer therapyR01CA142779 · NCI · JOHNS HOPKINS UNIVERSITY · PI PARDOLL, DREW M., TAUBE, JANIS M · 2010 to 2025
$8.2M
Understanding Inflammatory Arthritis due to Immune Checkpoint InhibitorsK23AR075872 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CAPPELLI, LAURA CHRISTINE · 2019 to 2023
$779k
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA142779NIAMS NIH HHS K23 AR075872NIAMS NIH HHS K23AR075872
6 · The paper itself

Abstract

backgroundTumor regression following immune checkpoint blockade (ICB) is often associated with immune-related adverse events (irAEs), marked by inflammation in non-cancerous tissues. This study was undertaken to investigate the functional relationship between anti-tumor and anti-self immunity, to facilitate irAE management while promoting anti-tumor immunity.

methodsMultiple biopsies from tumor and inflamed tissues were collected from a patient with melanoma experiencing both tumor regression and irAEs on ICB, who underwent rapid autopsy. Immune cells infiltrating melanoma lesions and inflamed normal tissues were subjected to gene expression profiling with multiplex qRT-PCR for 122 candidate genes. Subsequently, immunohistochemistry was conducted to assess the expression of 14 candidate markers of immune cell subsets and checkpoints. TCR-beta sequencing was used to explore T cell clonal repertoires across specimens.

resultsWhile genes involved in MHC I/II antigen presentation, IFN signaling, innate immunity and immunosuppression were abundantly expressed across specimens, irAE tissues over-expressed certain genes associated with immunosuppression (CSF1R, IL10RA, IL27/EBI3, FOXP3, KLRG1, SOCS1, TGFB1), including those in the COX-2/PGE2 pathway (IL1B, PTGER1/EP1 and PTGER4/EP4). Immunohistochemistry revealed similar proportions of immunosuppressive cell subsets and checkpoint molecules across samples. TCRseq did not indicate common TCR repertoires across tumor and inflammation sites, arguing against shared antigen recognition between anti-tumor and anti-self immunity in this patient.

conclusionsThis comprehensive study of a single patient with melanoma experiencing both tumor regression and irAEs on ICB explores the immune landscape across these tissues, revealing similarities between anti-tumor and anti-self immunity. Further, it highlights expression of the COX-2/PGE2 pathway, which is known to be immunosuppressive and potentially mediates ICB resistance. Ongoing clinical trials of COX-2/PGE2 pathway inhibitors targeting the major COX-2 inducer IL-1B, COX-2 itself, or the PGE2 receptors EP2 and EP4 present new opportunities to promote anti-tumor activity, but may also have the potential to enhance the severity of ICB-induced irAEs.

Indexed as

Blood Group AntigensMelanomaCyclooxygenase 2Cyclooxygenase 2 InhibitorsDinoprostoneHumansImmune Checkpoint InhibitorsInflammationReceptors, Antigen, T-CellBlood Group AntigensCyclooxygenase 2Cyclooxygenase 2 InhibitorsDinoprostoneImmune Checkpoint InhibitorsReceptors, Antigen, T-CellCOX-2Gene expression profiling (GEP)Immune checkpoint blockade (ICB)Immune related adverse events (irAEs)MelanomaRapid autopsyTumor infiltrating lymphocytes (TILs)

Identifiers

PMID38443917
PMCPMC10916264
OpenAlexW4392456254

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.