ArticleJournal for immunotherapy of cancer2022
Clinical outcome following checkpoint therapy in renal cell carcinoma is associated with a burst of activated CD8 T cells in blood.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The trial behind it
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Who cites it
31 citing papers in PubMed, 35 citations in OpenAlex.
- Dynamic immune profiling predicts response to radiation plus anti-PD-1 therapy in oligometastatic renal cell carcinoma.Nature communications · 2026Trial
- Simlukafusp alfa (FAP-IL2v) plus atezolizumab with or without bevacizumab in unresectable, metastatic renal cell carcinoma: a randomized, open-label phase Ib study.Journal for immunotherapy of cancer · 2026Trial
- Randomized pilot study of camrelizumab with or without autologous cytokine-induced killer cells in refractory clear cell renal cell carcinoma.Scientific reports · 2026Trial
- Lenvatinib plus transarterial chemoembolization and PD-1 inhibitors as conversion therapies for unresectable intermediate-advanced hepatocellular carcinoma: a phase 2 trial and exploratory biomolecular study.Signal transduction and targeted therapy · 2026Trial
- Peripheral blood biomarkers for predicting response to PD-1/PD-L1 inhibitors.Biomarker research · 2026Review
- Deciphering the mechanistic landscape of immune checkpoint blockade in ccRCC: from molecular drivers to therapeutic responses.Frontiers in immunology · 2026Review
- Immunological features of clear-cell renal-cell carcinoma and resistance to immune checkpoint inhibitors.Nature reviews. Nephrology · 2025Review
- Early-Phase Trial of IAP Antagonist Tolinapant and Definitive Radiation in Cisplatin-Ineligible Patients with Advanced Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Computed tomography-based radiomics predicts prognostic and treatment-related levels of immune infiltration in the immune microenvironment of clear cell renal cell carcinoma.BMC medical imaging · 2025Article
- Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8Signal transduction and targeted therapy · 2025Article
- Blood memory CD8 T cell phenotypes in lung cancer patients predict immune checkpoint treatment responses.Frontiers in oncology · 2025Article
- Immunogenic clearance combined with PD-1 blockade elicits antitumor effect by promoting the recruitment and expansion of the effector memory-like CD8Translational oncology · 2025Article
- Unlocking T cell exhaustion: Insights and implications for CAR-T cell therapy.Acta pharmaceutica Sinica. B · 2024Review
- Immunological profiling for short-term predictive analysis in PD-1/PD-L1 therapy for lung cancer.BMC cancer · 2024Article
- The pathogenic response of cytotoxic T‑lymphocytes, a common therapeutic target for cancer, has a direct impact on treatment outcomes (Review).Oncology reports · 2024Review
- Established and emerging biomarkers of immunotherapy in renal cell carcinoma.Immunotherapy · 2024Review
- Soluble lymphocyte activation gene-3 (sLAG3) and CD4/CD8 ratio dynamics as predictive biomarkers in patients undergoing immune checkpoint blockade for solid malignancies.British journal of cancer · 2024Article
- Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis.Journal for immunotherapy of cancer · 2024Article
- Management of Renal Cell Carcinoma: Promising Biomarkers and the Challenges to Reach the Clinic.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- The Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers.Biomarker insights · 2024Review
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
Abstract
purposeCheckpoint therapy is now the cornerstone of treatment for patients with renal cell carcinoma (RCC) with advanced disease, but biomarkers are lacking to predict which patients will benefit. This study proposes potential immunological biomarkers that could developed for predicting therapeutic response in patients with RCC.
methodsUsing flow cytometry, RNA sequencing, and T-cell receptor (TCR) sequencing, we investigated changes in T cells in the peripheral blood of patients with advanced RCC after receiving immunotherapy. We used immunofluorescence (IF) imaging and flow cytometry to investigate how intratumoral T cells in patients' tumors (resected months/years prior to receiving checkpoint therapy) predicted patient outcomes after immunotherapy.
resultsWe found that a small proportion of CD4 and CD8 T cells in the blood activate following checkpoint therapy, expressing the proliferation marker Ki67 and activation markers HLA-DR and CD38. Patients who had the highest increase in these HLA-DR +CD38+CD8 T cells after treatment had the best antitumor immune response and experienced clinical benefit. Using RNA sequencing, we found that while these cells expanded in most patients, their phenotype did not drastically change during treatment. However, when we analyzed the TCR repertoire of these HLA-DR +CD38+CD8+T cells, we found that only patients who clinically benefitted had a burst of new clonotypes enter this pool of activated cells. Finally, we found that abundant T cells in the untreated tumors predicted clinical benefit to checkpoint therapy on disease progression.
conclusionsTogether, these data suggest that having a strong pre-existing immune response and immediate peripheral T-cell activation after checkpoint therapy is a predictor of clinical benefit in patients with RCC.
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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.