Evidence map›Paper›PMID 40499464›Full record

ArticleESMO open2025

Uncovering PD-L1 among immune cell predictive biomarkers and actionable genetic alterations in anal squamous-cell carcinomas in the era of immunotherapy.

G Sharma, Y Baca, A F Shields, A Prakash, B A Weinberg, A Saeed, S Goel, A Abdalla, M Oberley, J Xiu and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Trial
  2. Article
  3. 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

14 authors.

G SharmaDivision of Hematology and Medical Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, USA.
Y BacaCARIS Life Sciences, Phoenix, USA.
A F ShieldsBarbara Ann Karmanos Cancer Institute, Detroit, USA.
A PrakashDepartment of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, USA.
B A WeinbergLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, USA.
A SaeedDivision of Hematology/Oncology, University of Pittsburgh, Pittsburgh, USA.
S GoelRutgers Cancer Institute of New Jersey, New Brunswick, USA.
A AbdallaDivision of Hematology and Medical Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, USA.
M OberleyCARIS Life Sciences, Phoenix, USA.
J XiuCARIS Life Sciences, Phoenix, USA.
J HwangDepartment of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, USA.
E S AntonarakisDepartment of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, USA.
V K ChiuThe Angeles Clinic and Research Institute, a Cedars-Sinai affiliate, Los Angeles, USA.
E LouDepartment of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, USA; Graduate Faculty, Integrative Biology and Physiology Department, University of Minnesota, Minneapolis, USA. Electronic address: Emil-lou@umn.edu.

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
NCI NIH HHS P30 CA077598
6 · The paper itself

Abstract

backgroundAnal squamous-cell carcinoma (ASCC) is a rare cancer. Immune checkpoint inhibitors (ICIs) are used as a second-line treatment. We aimed to analyze the genomic and transcriptomic profiles of ASCC to predict ICI efficacy. MATERIALS AND

methodsNext-generation sequencing (NGS) of DNA and RNA was carried out. Programmed death- ligand 1 (PD-L1) expression was tested by immunohistochemistry (IHC) as high (≥2+ and ≥5%), low (1-2+ and ≥1%), and negative (<1). Deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) was tested using IHC/NGS, and tumor mutation burden-high (TMB-H) was defined as ≥10 mutations/Mb. quanTIseq was used to quantify tumor microenvironment. The chi-square test / Fisher's exact test was used, and significance was determined as P value adjusted for multiple comparisons (q < 0.05). Real-world overall survival and time on treatment (TOT) were obtained from insurance claims.

resultsOut of 1242 tumor samples, 64.25% expressed PD-L1, with 41.7% exhibiting high expression. TMB-H and dMMR/MSI-H prevalence rates were 11.43% and 1.04%, respectively. TMB-H tended to be higher in PD-L1-low versus PD-L1-negative patients (P = 0.03). Mutations in PIK3CA and CASP8 were significantly higher in PD-L1-high versus -negative. PD-L1-high tumor microenvironment showed higher infiltration of Tregs, M1 macrophages, neutrophils, CD8 cells, and cancer-associated fibroblasts compared with PD-L1-low (q < 0.05). The expression of immuno-oncology (IO) markers, including IDO1, PDCD1, IFNG, CD274, HVACR2, CTLA4, LAG3, CD80, CD86, and PDCD1LG2, as well as T-cell inflammation and interferon-gamma scores, exhibited a concurrent decline in association with PD-L1 expression. The PD-L1-high group treated with ICIs had significantly longer TOT than the PD-L1-negative group (hazard ratio 0.758, 95% confidence interval 0.579-0.992, P = 0.044).

conclusionPD-L1-expressing ASCCs exhibit higher rates of PIK3CA and CASP8 mutations, increased IO markers, and higher inflammation. These tumors had longer treatment durations when treated with ICIs, suggesting that PD-L1 expression predicts treatment response.

Indexed as

Anus NeoplasmsB7-H1 AntigenBiomarkers, TumorCarcinoma, Squamous CellImmunotherapyAdultAgedFemaleHumansImmune Checkpoint InhibitorsMaleMicrosatellite InstabilityMiddle AgedMutationTumor MicroenvironmentB7-H1 AntigenBiomarkers, TumorCD274 protein, humanImmune Checkpoint Inhibitorsanal squamous-cell carcinomagastrointestinal cancerimmune checkpoint inhibitorprogrammed death-ligand 1tumor immune microenvironmenttumor mutation burden

Identifiers

PMID40499464
PMCPMC12182785

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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.