ArticleCancer research2014
Immunosuppressive myeloid cells induced by chemotherapy attenuate antitumor CD4+ T-cell responses through the PD-1-PD-L1 axis.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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.
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
79 citing papers in PubMed, 130 citations in OpenAlex.
- A Phase II Trial to Evaluate the Safety and Immunogenicity of Two Doses of a Folate Receptor Alpha Vaccine in Patients with Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Topical Imiquimod Plus Nab-paclitaxel for Breast Cancer Cutaneous Metastases: A Phase 2 Clinical Trial.JAMA oncology · 2017Trial
- A randomized phase II trial of personalized peptide vaccine with low dose cyclophosphamide in biliary tract cancer.Cancer science · 2017Trial
- Chemotherapy-induced reactive myelopoiesis promotes expansion of immunosuppressive neutrophil-like monocytes in mice and humans.JCI insight · 2026Article
- Immune-Enhancement Effects of 6-Methoxykaempferol on Cyclophosphamide-Induced Immunosuppression via Improving Antioxidant Enzyme Expression, NF-κB and MAPK Signaling, and Modulating Gut Microbiome.Antioxidants (Basel, Switzerland) · 2026Article
- Cyclophosphamide-Mediated Induction of Myeloid-Derived Suppressor Cells In Vivo: Kinetics of Accumulation, Immune Profile, and Immunomodulation by Oleanane-Type Triterpenoids.International journal of molecular sciences · 2026Article
- Nonpolysaccharide fraction ofFrontiers in pharmacology · 2026Article
- CMTM6/PD-L1-targeted AAV promotes anti-tumor immune responses and chemotherapy responsiveness.Frontiers in immunology · 2026Article
- Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.MedComm · 2025Review
- Enhancing the sensitivity of lung adenocarcinoma to immune therapeutic agents throughTranslational lung cancer research · 2025Article
- Investigating the Synergistic Effects of Pembrolizumab and Chemotherapy in Gastric and Gastroesophageal Junction Cancer.Journal of gastric cancer · 2025Article
- Investigating the synergistic effects of immunochemotherapy in esophageal squamous cell carcinoma.Esophagus : official journal of the Japan Esophageal Society · 2025Article
- Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors.Cellular & molecular immunology · 2025Review
- Adenosine Increases the Immunosuppressive Capacity of Cervical Cancer Cells by Increasing PD-L1 Expression and TGF-β Production through Its Interaction with APharmaceuticals (Basel, Switzerland) · 2024Article
- Sorafenib inhibits doxorubicin-induced PD-L1 upregulation to improve immunosuppressive microenvironment in Osteosarcoma.Journal of cancer research and clinical oncology · 2023Article
- Chemo-Immunotherapy: A New Trend in Cancer Treatment.Cancers · 2023Review
- Metformin improves cancer immunotherapy by directly rescuing tumor-infiltrating CD8 T lymphocytes from hypoxia-induced immunosuppression.Journal for immunotherapy of cancer · 2023Article
- PD-L1 induction via the MEK-JNK-AP1 axis by a neddylation inhibitor promotes cancer-associated immunosuppression.Cell death & disease · 2022Article
- Grain-Sized Moxibustion Heightens the AntiTumor Effect of Cyclophosphamide in Hepa1-6 Bearing Mice.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Unveiling the Noncanonical Autophagy-Independent Role ofJournal of oncology · 2022Article
19 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
14 authors at 6 institutions in 4 countries.
Funding
Abstract
In recent years, immune-based therapies have become an increasingly attractive treatment option for patients with cancer. Cancer immunotherapy is often used in combination with conventional chemotherapy for synergistic effects. The alkylating agent cyclophosphamide (CTX) has been included in various chemoimmunotherapy regimens because of its well-known immunostimulatory effects. Paradoxically, cyclophosphamide can also induce suppressor cells that inhibit immune responses. However, the identity and biologic relevance of these suppressor cells are poorly defined. Here we report that cyclophosphamide treatment drives the expansion of inflammatory monocytic myeloid cells (CD11b(+)Ly6C(hi)CCR2(hi)) that possess immunosuppressive activities. In mice with advanced lymphoma, adoptive transfer (AT) of tumor-specific CD4(+) T cells following cyclophosphamide treatment (CTX+CD4 AT) provoked a robust initial antitumor immune response, but also resulted in enhanced expansion of monocytic myeloid cells. These therapy-induced monocytes inhibited long-term tumor control and allowed subsequent relapse by mediating functional tolerization of antitumor CD4(+) effector cells through the PD-1-PD-L1 axis. PD-1/PD-L1 blockade after CTX+CD4 AT therapy led to persistence of CD4(+) effector cells and durable antitumor effects. Depleting proliferative monocytes by administering low-dose gemcitabine effectively prevented tumor recurrence after CTX+CD4 AT therapy. Similarly, targeting inflammatory monocytes by disrupting the CCR2 signaling pathway markedly potentiated the efficacy of cyclophosphamide-based therapy. Besides cyclophosphamide, we found that melphalan and doxorubicin can also induce monocytic myeloid suppressor cells. These findings reveal a counter-regulation mechanism elicited by certain chemotherapeutic agents and highlight the importance of overcoming this barrier to prevent late tumor relapse after chemoimmunotherapy.
Indexed as
Identifiers
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.