Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2011
CTLA4 blockade induces frequent tumor infiltration by activated lymphocytes regardless of clinical responses in humans.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
96 citing papers in PubMed, 2 syntheses or guidelines pooled it, 151 citations in OpenAlex.
- Pooled it
- Biomarkers, measured during therapy, for response of melanoma patients to immune checkpoint inhibitors: a systematic review.Melanoma research · 2019Pooled it
- Tremelimumab with or without durvalumab in combination with paclitaxel in metastatic urothelial cancer: phase I/II ICRA trial.Nature communications · 2026Trial
- Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: a randomized phase 2 trial.Nature medicine · 2023Trial
- Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- Clonotypic Diversification of Intratumoral T Cells Following Sipuleucel-T Treatment in Prostate Cancer Subjects.Cancer research · 2016Trial
- Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial.The Lancet. Oncology · 2015Trial
- Activated lymphocyte recruitment into the tumor microenvironment following preoperative sipuleucel-T for localized prostate cancer.Journal of the National Cancer Institute · 2014Trial
- Multifunctional T-cell analyses to study response and progression in adoptive cell transfer immunotherapy.Cancer discovery · 2013Trial
- Unraveling Th subsets: insights into their role in immune checkpoint inhibitor therapy.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3Nature communications · 2024Article
- Efficacy and prognostic factors of anti-PD1 and nivolumab-ipilimumab therapy in advanced melanoma patients resistant to prior ICI treatment.Discover oncology · 2024Article
- Review
- Exploring the safety profile of tremelimumab: an analysis of the FDA adverse event reporting system.International journal of clinical pharmacy · 2024Article
- Progress of Immune Checkpoint Inhibitors Therapy for pMMR/MSS Metastatic Colorectal Cancer.OncoTargets and therapy · 2024Review
- Turning up the heat: CTLA4 blockade in urothelial cancer.Nature reviews. Urology · 2024Review
- Locally advanced endometrial cancer with multiple immune-related adverse events coinciding with the complete response to radiotherapy after immune checkpoint inhibitor therapy: A case report.Gynecologic oncology reports · 2023Article
- Prior anti-CTLA-4 therapy impacts molecular characteristics associated with anti-PD-1 response in advanced melanoma.Cancer cell · 2023Article
- Barriers to immune cell infiltration in tumors.Journal for immunotherapy of cancer · 2023Review
- Adverse events induced by durvalumab and tremelimumab combination regimens: a systematic review and meta-analysis.Therapeutic advances in medical oncology · 2023Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCTLA4 blocking monoclonal antibodies provide durable clinical benefit in a subset of patients with advanced melanoma mediated by intratumoral lymphocytic infiltrates. A key question is defining whether the intratumoral infiltration (ITI) is a differentiating factor between patients with and without tumor responses.
methodsPaired baseline and postdosing tumor biopsy specimens were prospectively collected from 19 patients with metastatic melanoma, including 3 patients with an objective tumor response, receiving the anti-CTLA4 antibody tremelimumab within a clinical trial with primary endpoint of quantitating CD8(+) cytotoxic T-lymphocyte (CTL) infiltration in tumors. Samples were analyzed for cell density by automated imaging capture and further characterized for functional lymphocyte properties by assessing the cell activation markers HLA-DR and CD45RO, the cell proliferation marker Ki67, and the regulatory T-cell marker FOXP3.
resultsThere was a highly significant increase in ITI by CD8(+) cells in biopsy samples taken after tremelimumab treatment. This included increases between 1-fold and 100-fold changes in 14 of 18 evaluable cases regardless of clinical tumor response or progression. There was no difference between the absolute number, location, or cell density of infiltrating cells between clinical responders and patients with nonresponding lesions that showed acquired intratumoral infiltrates. There were similar levels of expression of T-cell activation markers (CD45RO, HLA-DR) in both groups and no difference in markers for cell replication (Ki67) or the suppressor cell marker FOXP3.
conclusionCTLA4 blockade induces frequent increases in ITI by T cells despite which only a minority of patients have objective tumor responses.
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What OpenQuestion holds
Registered trials
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.