ArticleProceedings of the National Academy of Sciences of the United States of America2017
Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 276 papers.
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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.
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Who cites it
276 citing papers in PubMed, 399 citations in OpenAlex.
- Tumor-Regional Immune Microenvironment: A Critical Factor in the Design of Radiotherapy-Immunotherapy Combination Trials.International journal of cancer · 2026Review
- Mitochondrial transfer-driven immune evasion in the tumor microenvironment.International immunology · 2026Review
- Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review).Oncology reports · 2026Review
- Emerging roles of ferroptosis in modulating the immune landscape of glial tumours.Nature cell biology · 2026Review
- Patient-specific lung cancer tumoroids recapitulate the tumor microenvironments for functional evaluation of therapeutic responses and immune-stromal interactions.Journal of translational medicine · 2026Article
- Supervised deep learning with gene functional annotation for cell classification.PLoS computational biology · 2026Article
- Multifunctional Role of Mitochondrial Fatty Acid Oxidation in Cancer Immunotherapy and Aging.Cancer science · 2026Review
- Limited Immune-Mediated Efficacy of Anti-PD-L1/VEGF in EGFR-TKI-NaïveCurrent oncology (Toronto, Ont.) · 2026Article
- Lactate signaling and immune suppression in tumors: mechanisms and therapeutic implications.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Mitochondria in T‑cell tumor immunity and tumor therapies targeting mitochondria (Review).Oncology reports · 2026Review
- Review
- Targeting fatty acid metabolism for cancer therapy.Fundamental research · 2026Review
- T-Cell Immunity and Lung Cancer.Respirology (Carlton, Vic.) · 2026Review
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- Unraveling Immune Checkpoint Inhibitor-Associated Cardiovascular Toxicities: Pathway Insights, Mechanisms, and Emerging Therapeutic Targets.Reviews in cardiovascular medicine · 2026Review
- Mitochondrial antioxidant enzyme (SOD2) at the crossroads of redox signaling and cancer progression.Free radical research · 2026Review
- Active aldehydes accelerate CD8Nature immunology · 2026Article
- Cancer and Immune Cells: A Metabolic Battle in the Tumor Microenvironment.Cancer treatment and research · 2026Review
- Mitochondrial Energy Metabolism in Cancer, Immunoregulation and Antitumour Response.Advances in experimental medicine and biology · 2026Review
- Mitochondrial transfer: a new perspective on tumor-microenvironment crosstalk driving metastasis.Frontiers in immunology · 2026Review
216 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
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although immunotherapy by PD-1 blockade has dramatically improved the survival rate of cancer patients, further improvement in efficacy is required to reduce the fraction of less sensitive patients. In mouse models of PD-1 blockade therapy, we found that tumor-reactive cytotoxic T lymphocytes (CTLs) in draining lymph nodes (DLNs) carry increased mitochondrial mass and more reactive oxygen species (ROS). We show that ROS generation by ROS precursors or indirectly by mitochondrial uncouplers synergized the tumoricidal activity of PD-1 blockade by expansion of effector/memory CTLs in DLNs and within the tumor. These CTLs carry not only the activation of mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) but also an increment of their downstream transcription factors such as PPAR-gamma coactivator 1α (PGC-1α) and T-bet. Furthermore, direct activators of mTOR, AMPK, or PGC-1α also synergized the PD-1 blockade therapy whereas none of above-mentioned chemicals alone had any effects on tumor growth. These findings will pave a way to developing novel combinatorial therapies with PD-1 blockade.
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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.