CoChat
Sign Up
Cited by 375

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Synergistic and low adverse effect cancer immunotherapy by immunogenic chemotherapy and locally expressed PD-L1 trap

Song, Wantong, Shen, Limei, Wang, Ying, Liu, Qi, Goodwin, Tyler J., Li, Jingjing, Dorosheva, Olekasandra, Liu, Tianzhou, Liu, Rihe, Huang, Leaf·2018·Nature Communications
DOI 10.1038/s41467-018-04605-xPMC PMC5993831
Open this paper in CoChat — free account

Abstract

Although great success has been obtained in the clinic, the current immune checkpoint inhibitors still face two challenging problems: low response rate and immune-related adverse effects (irAEs). Here we report the combination of immunogenic chemotherapy and locally expressed PD-L1 trap fusion protein for efficacious and safe cancer immunotherapy. We demonstrate that oxaliplatin (OxP) boosts anti-PD-L1 mAb therapy against murine colorectal cancer. By design of a PD-L1 trap and loading its coding plasmid DNA into a lipid-protamine-DNA nanoparticle, PD-L1 trap is produced transiently and locally in the tumor microenvironment, and synergizes with OxP for tumor inhibition. Significantly, unlike the combination of OxP and anti-PD-L1 mAb, the combination of OxP and PD-L1 trap does not induce obvious Th17 cells accumulation in the spleen, indicating better tolerance and lower tendency to irAEs. The reports here may highlight the potential of applying PD-L1 inhibitor, especially locally expressed PD-L1 trap, in cancer therapy following OxP-based chemotherapy.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-018-04605-x

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1 Orthotopic CT26-FL3 tumor is resistant to anti-PD-L1 mAb therapy. a Establishment of orthotopic colorectal tumor models. CT26-FL3 (RFP/Luc) cells were inoculated into the mouse cecum wall, and the tumor burden was monitored by bioluminescent analysis. b Treatment scheme and tumor growth curves of orthotopic CT26-FL3 tumors in PBS and α-PD-L1 treated groups (n = 5 mice per group). c Masson’s trichrome and immunofluorescence staining of orthotopic CT26-FL3 tumor tissues in PBS group using 4′,6-diamidino-2-phenylindole (DAPI, blue) and anti-CD3 antibody (red). Yellow dotted line indicates the border between intestinal mucosa and the orthotopic tumor. Scale bar represents 50 μm. Significant differences were assessed in b using two-way ANOVA. Results are presented as mean (SD). ns, not significant
Fig. 1 Orthotopic CT26-FL3 tumor is resistant to anti-PD-L1 mAb therapy. a Establishment of orthotopic colorectal tumor models. CT26-FL3 (RFP/Luc) cells were inoculated into the mouse cecum wall, and the tumor burden was monitored by bioluminescent analysis. b Treatment scheme and tumor growth curves of orthotopic CT26-FL3 tumors in PBS and α-PD-L1 treated groups (n = 5 mice per group). c Masson’s trichrome and immunofluorescence staining of orthotopic CT26-FL3 tumor tissues in PBS group using 4′,6-diamidino-2-phenylindole (DAPI, blue) and anti-CD3 antibody (red). Yellow dotted line indicates the border between intestinal mucosa and the orthotopic tumor. Scale bar represents 50 μm. Significant differences were assessed in b using two-way ANOVA. Results are presented as mean (SD). ns, not significantCC BY · PubMed Central
Fig. 2 OxP induces ICD in the CT26-FL3 tumor. a OxP treatment scheme. b Immunofluorescence staining of orthotopic CT26-FL3 tumors after PBS and OxP treatment using DAPI (blue), anti-HMGB1 antibody (red), and anti-CRT antibody (red). Positive ratios were quantified in 5 randomly selected fields per mouse (n = 4 mice per group). Yellow dotted line indicates the border between intestinal mucosa and the orthotopic tumor. Scale bar represents 50 μm. c ELISpot test of the splenocytes of CT26-FL3 tumor-bearing mice after PBS and OxP treatment. Significant differences were assessed in b using t test. Results are presented as mean (SD). **P < 0.01, ***P < 0.001
Fig. 2 OxP induces ICD in the CT26-FL3 tumor. a OxP treatment scheme. b Immunofluorescence staining of orthotopic CT26-FL3 tumors after PBS and OxP treatment using DAPI (blue), anti-HMGB1 antibody (red), and anti-CRT antibody (red). Positive ratios were quantified in 5 randomly selected fields per mouse (n = 4 mice per group). Yellow dotted line indicates the border between intestinal mucosa and the orthotopic tumor. Scale bar represents 50 μm. c ELISpot test of the splenocytes of CT26-FL3 tumor-bearing mice after PBS and OxP treatment. Significant differences were assessed in b using t test. Results are presented as mean (SD). **P < 0.01, ***P < 0.001CC BY · PubMed Central
Fig. 3 OxP induces immune microenvironment changes and synergizes with α-PD-L1 in CT26-FL3 tumor therapy. a CD8+ T cells, CD4+ T cells, activated DCs and PD-L1 levels in tumors of the PBS and OxP-treated groups on day 28, analyzed by flow cytometry (n = 4). b Relative mRNA expressions of various cytokines in tumors of the OxP-treated group compared to PBS group on day 28, detected by quantitative RT-PCR (n = 4). c Masson’s trichrome and immunofluorescence staining of the orthotopic tumors after OxP treatment using DAPI (blue), anti-CD3 (red), anti-CD11c (red), anti-CD274 (red), and anti-IL-10 (red). Yellow dotted line indicates the border between intestinal mucosa and the orthotopic tumor. Scale bar represents 50 μm. d Treatment scheme and tumor growth curves of orthotopic CT26-FL3 tumors in PBS, α-PD-L1, OxP, and OxP + α-PD-L1 treated groups (n = 5 mice per group). e Th17 cell ratios in the splenocytes of the mice after various treatments on day 28 (n = 4). Significant differences were assessed in d using two-way ANOVA with multiple comparisons and in a, b, and e using t test. Results are presented as mean (SD). ns not significant. *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 3 OxP induces immune microenvironment changes and synergizes with α-PD-L1 in CT26-FL3 tumor therapy. a CD8+ T cells, CD4+ T cells, activated DCs and PD-L1 levels in tumors of the PBS and OxP-treated groups on day 28, analyzed by flow cytometry (n = 4). b Relative mRNA expressions of various cytokines in tumors of the OxP-treated group compared to PBS group on day 28, detected by quantitative RT-PCR (n = 4). c Masson’s trichrome and immunofluorescence staining of the orthotopic tumors after OxP treatment using DAPI (blue), anti-CD3 (red), anti-CD11c (red), anti-CD274 (red), and anti-IL-10 (red). Yellow dotted line indicates the border between intestinal mucosa and the orthotopic tumor. Scale bar represents 50 μm. d Treatment scheme and tumor growth curves of orthotopic CT26-FL3 tumors in PBS, α-PD-L1, OxP, and OxP + α-PD-L1 treated groups (n = 5 mice per group). e Th17 cell ratios in the splenocytes of the mice after various treatments on day 28 (n = 4). Significant differences were assessed in d using two-way ANOVA with multiple comparisons and in a, b, and e using t test. Results are presented as mean (SD). ns not significant. *P < 0.05, **P < 0.01, ***P < 0.001CC BY · PubMed Central
Fig. 4 Design of locally and transiently expressed PD-L1 trap. a Scheme showing the tribody interaction of PD-L1 trap protein. b Preparation scheme of PD-L1 trap plasmid loaded LPD. c Images and quantitative results of the DiI-loaded LPD in major organs and the CT26-FL3 tumor at 24 h after injection (n = 3). d PD-L1 trap protein expression in major organs and the CT26-FL3 tumor at 48 h after injection. The PD-L1 trap expression was measured using ELISA by targeting the His (6×)-tag engineered at the C-terminus of the PD-L1 trap (n = 3). e PD-L1 trap protein expression in tumors on days 1, 2, 4 and 7 after injection. Significant differences in c, d, and e were assessed using t test. Results are presented as mean (SD). ns, not significant. *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 4 Design of locally and transiently expressed PD-L1 trap. a Scheme showing the tribody interaction of PD-L1 trap protein. b Preparation scheme of PD-L1 trap plasmid loaded LPD. c Images and quantitative results of the DiI-loaded LPD in major organs and the CT26-FL3 tumor at 24 h after injection (n = 3). d PD-L1 trap protein expression in major organs and the CT26-FL3 tumor at 48 h after injection. The PD-L1 trap expression was measured using ELISA by targeting the His (6×)-tag engineered at the C-terminus of the PD-L1 trap (n = 3). e PD-L1 trap protein expression in tumors on days 1, 2, 4 and 7 after injection. Significant differences in c, d, and e were assessed using t test. Results are presented as mean (SD). ns, not significant. *P < 0.05, **P < 0.01, ***P < 0.001CC BY · PubMed Central
Fig. 5 Combination of OxP and LPD-PD-L1 trap gene therapy on orthotopic CT26-FL3 tumor model. a OxP and PD-L1 trap combination treatment scheme. b Tumor growth curves of orthotopic CT26-FL3 tumors in PBS, LPD-pGFP, PD-L1 trap, OxP and OxP+PD-L1 trap gene treated groups (n = 5 mice per group). c TSR% results on day 35. d Mice survival curves. e CD8+ T cells, CD4+ T cells, activated DCs and PD-L1 levels in tumors of mice after various treatments, analyzed by flow cytometry (n = 4). f Masson’s trichrome and immunofluorescence staining of the orthotopic tumors after OxP+PD-L1 trap treatment using DAPI (blue) and anti-CD3 (red). Yellow dotted line indicates the border between intestinal mucosa and the orthotopic tumor. Scale bar represents 50 μm. g Relative mRNA expressions of cytokines in tumors of the OxP+PD-L1 trap treated group compared to PBS group on day 28, detected by quantitative RT-PCR (n = 4). h Th17 cell ratios in the splenocytes of mice after various treatments on day 28 (n = 4). Significant differences were assessed in b using two-way ANOVA with multiple comparisons, in d using log rank test and in c, e, g, and h using t test. Results are presented as mean (SD). ns, not significant. *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 5 Combination of OxP and LPD-PD-L1 trap gene therapy on orthotopic CT26-FL3 tumor model. a OxP and PD-L1 trap combination treatment scheme. b Tumor growth curves of orthotopic CT26-FL3 tumors in PBS, LPD-pGFP, PD-L1 trap, OxP and OxP+PD-L1 trap gene treated groups (n = 5 mice per group). c TSR% results on day 35. d Mice survival curves. e CD8+ T cells, CD4+ T cells, activated DCs and PD-L1 levels in tumors of mice after various treatments, analyzed by flow cytometry (n = 4). f Masson’s trichrome and immunofluorescence staining of the orthotopic tumors after OxP+PD-L1 trap treatment using DAPI (blue) and anti-CD3 (red). Yellow dotted line indicates the border between intestinal mucosa and the orthotopic tumor. Scale bar represents 50 μm. g Relative mRNA expressions of cytokines in tumors of the OxP+PD-L1 trap treated group compared to PBS group on day 28, detected by quantitative RT-PCR (n = 4). h Th17 cell ratios in the splenocytes of mice after various treatments on day 28 (n = 4). Significant differences were assessed in b using two-way ANOVA with multiple comparisons, in d using log rank test and in c, e, g, and h using t test. Results are presented as mean (SD). ns, not significant. *P < 0.05, **P < 0.01, ***P < 0.001CC BY · PubMed Central
Fig. 6 OxP and LPD-PD-L1 trap gene therapy on B16F10 and 4T1 tumor models. a Treatment scheme and tumor growth curves of B16F10 tumors in PBS, PD-L1 trap, OxP and OxP + PD-L1 trap treated groups (n = 5 mice per group). b Treatment scheme and tumor growth curves of 4T1 tumors in PBS, PD-L1 trap, OxP and OxP + PD-L1 trap treated groups (n = 5 mice per group). c CD4+ and CD8+ T cell ratios in the B16F10 tumors after various treatments, analyzed by flow cytometry (n = 4). d CD4+ T cell, CD8+ T cell and Th17 cell ratios in splenocytes of the B16F10 tumor-bearing mice after various treatments, analyzed by flow cytometry (n = 4). e CD4+ and CD8+ T cell ratios in the 4T1 tumors after various treatments, analyzed by flow cytometry (n = 4). f CD4+ T cell, CD8+ T cell and Th17 cell ratios in splenocytes of the 4T1 tumor-bearing mice after various treatments, analyzed by flow cytometry (n = 4). Significant differences were assessed in a and b using two-way ANOVA with multiple comparisons and in c, d, e, and f using t test. Results are presented as mean (SD). ns, not significant. *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 6 OxP and LPD-PD-L1 trap gene therapy on B16F10 and 4T1 tumor models. a Treatment scheme and tumor growth curves of B16F10 tumors in PBS, PD-L1 trap, OxP and OxP + PD-L1 trap treated groups (n = 5 mice per group). b Treatment scheme and tumor growth curves of 4T1 tumors in PBS, PD-L1 trap, OxP and OxP + PD-L1 trap treated groups (n = 5 mice per group). c CD4+ and CD8+ T cell ratios in the B16F10 tumors after various treatments, analyzed by flow cytometry (n = 4). d CD4+ T cell, CD8+ T cell and Th17 cell ratios in splenocytes of the B16F10 tumor-bearing mice after various treatments, analyzed by flow cytometry (n = 4). e CD4+ and CD8+ T cell ratios in the 4T1 tumors after various treatments, analyzed by flow cytometry (n = 4). f CD4+ T cell, CD8+ T cell and Th17 cell ratios in splenocytes of the 4T1 tumor-bearing mice after various treatments, analyzed by flow cytometry (n = 4). Significant differences were assessed in a and b using two-way ANOVA with multiple comparisons and in c, d, e, and f using t test. Results are presented as mean (SD). ns, not significant. *P < 0.05, **P < 0.01, ***P < 0.001CC BY · PubMed Central
Fig. 7 MSS colorectal cancer patient sample analysis. a Representative immunohistochemistry images of tumor tissues from MSS colorectal cancer patients. Untreated represents samples from patients without any therapy. XELOX represents samples from patients after XELOX neoadjuvant chemotherapy. Images are taken at ×40 magnification. Dark red circles indicate the hot spots in each visual field. b Statistics of hot spots in each visual field (n = 4 samples per group). c Representative immunofluorescence images of tumor tissues using DAPI (blue) and anti-CD3 (red). Yellow dotted line indicates the border between intestinal mucosa and the tumor. Scale bar represents 50 μm. d Statistics of CD3+ T cell ratios in each slice (n = 5 samples per group). Significant differences were assessed in b and d using t test. Results are presented as mean (SD). **P < 0.01, ***P < 0.001
Fig. 7 MSS colorectal cancer patient sample analysis. a Representative immunohistochemistry images of tumor tissues from MSS colorectal cancer patients. Untreated represents samples from patients without any therapy. XELOX represents samples from patients after XELOX neoadjuvant chemotherapy. Images are taken at ×40 magnification. Dark red circles indicate the hot spots in each visual field. b Statistics of hot spots in each visual field (n = 4 samples per group). c Representative immunofluorescence images of tumor tissues using DAPI (blue) and anti-CD3 (red). Yellow dotted line indicates the border between intestinal mucosa and the tumor. Scale bar represents 50 μm. d Statistics of CD3+ T cell ratios in each slice (n = 5 samples per group). Significant differences were assessed in b and d using t test. Results are presented as mean (SD). **P < 0.01, ***P < 0.001CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 6 references

Research works printed but not linked: 44

  1. Yarchoan, M., Johnson, B. A. 3rd, Lutz, E. R., Laheru, D. A. & Jaffee, E. M. Targeting neoantigens to augment antitumour immunity. Nat. Rev. Cancer 17, 209–222 (2017). · DOI · Paper page
  2. Kroemer, G., Galluzzi, L., Kepp, O. & Zitvogel, L. Immunogenic cell death in cancer therapy. Annu. Rev. Immunol. 31, 51–72 (2013). · DOI · Paper page
  3. Galluzzi, L., Buque, A., Kepp, O., Zitvogel, L. & Kroemer, G. Immunogenic cell death in cancer and infectious disease. Nat. Rev. Immunol. 17, 97–111 (2017). · DOI · Paper page
  4. Griswold, D. P. & Corbett, T. H. A colon tumor model for anticancer agent evaluation. Cancer 36, 2441–2444 (1975). · DOI
  5. Castle, J. C. et al. Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma. BMC Genom. 15, 190 (2014). · DOI
  6. Germano, G. et al. Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth. Nature 552, 116 (2017). · DOI
  7. Zhang, Y., Davis, C., Ryan, J., Janney, C. & Pena, M. M. Development and characterization of a reliable mouse model of colorectal cancer metastasis to the liver. Clin. Exp. Metastas. 30, 903–918 (2013). · DOI
  8. Efremova, M. et al. Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution. Nat. Commun. 9, 32 (2018). · DOI
  9. Tesniere, A. et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene 29, 482–491 (2010). · DOI
  10. Hato, S. V., Khong, A., de Vries, I. J. & Lesterhuis, W. J. Molecular pathways: the immunogenic effects of platinum-based chemotherapeutics. Clin. Cancer Res. 20, 2831–2837 (2014). · DOI
  11. Scrimieri, F. et al. Murine leukemia virus envelope gp70 is a shared biomarker for the high-sensitivity quantification of murine tumor burden. Oncoimmunology 2, e26889 (2013). · DOI
  12. Goodwin, T. J. & Huang, L. Investigation of phosphorylated adjuvants co-encapsulated with a model cancer peptide antigen for the treatment of colorectal cancer and liver metastasis. Vaccine 35, 2550–2557 (2017). · DOI
  13. Hu, J., Bernatchez, C., Xia, X., Xu, Z. and Hwu, P. CXCL9, CXCL10 and IFNγ favor the accumulation of infused T cells in tumors following IL-12 plus doxorubicin treatment. J. Immunol. 196, 211–212.1 (2016). · DOI
  14. Pitzalis, C., Jones, G. W., Bombardieri, M. & Jones, S. A. Ectopic lymphoid-like structures in infection, cancer and autoimmunity. Nat. Rev. Immunol. 14, 447–462 (2014). · DOI
  15. Di Caro, G. et al. Occurrence of tertiary lymphoid tissue is associated with T-cell infiltration and predicts better prognosis in early-stage colorectal cancers. Clin. Cancer Res. 20, 2147–2158 (2014). · DOI
  16. Finkin, S. et al. Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat. Immunol. 16, 1235–1244 (2015). · DOI · Paper page
  17. Zhu, S. & Qian, Y. IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clin. Sci. 122, 487–511 (2012). · DOI
  18. Yamada, H. Current perspectives on the role of IL-17 in autoimmune disease. J. Inflamm. Res. 3, 33–44 (2010). · DOI
  19. Yshii, L. M., Hohlfeld, R. & Liblau, R. S. Inflammatory CNS disease caused by immune checkpoint inhibitors: status and perspectives. Nat. Rev. Neurol. 13, 755 (2017). · DOI
  20. Naidoo, J. et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann. Oncol. 26, 2375–2391 (2015). · DOI
  21. Kim, D., Kim, S. K., Valencia, C. A. & Liu, R. Tribody: robust self-assembled trimeric targeting ligands with high stability and significantly improved target-binding strength. Biochemistry 52, 7283–7294 (2013). · DOI
  22. Goodwin, T. J. et al. Liver specific gene immunotherapies resolve immune suppressive ectopic lymphoid structures of liver metastases and prolong survival. Biomaterials 141, 260–271 (2017). · DOI
  23. Li, S. D. & Huang, L. Surface-modified LPD nanoparticles for tumor targeting. Ann. N. Y. Acad. Sci. 1082, 1–8 (2006). · DOI
  24. Wang, Y. et al. Systemic delivery of modified mRNA encoding herpes simplex virus 1 thymidine kinase for targeted cancer gene therapy. Mol. Ther. 21, 358–367 (2013). · DOI
  25. Miao, L. et al. Transient and local expression of chemokine and immune checkpoint traps to treat pancreatic cancer. ACS Nano 11, 8690–8706 (2017). · DOI
  26. Castle, J. C. et al. Mutated tumor alleles are expressed according to their DNA frequency. Sci. Rep. 4, 4743 (2014). · DOI
  27. Chen, L. et al. Rejection of metastatic 4T1 breast cancer by attenuation of Treg cells in combination with immune stimulation. Mol. Ther. 15, 2194–2202 (2007). · DOI
  28. Celik, C., Lewis, D. A. & Goldrosen, M. H. Demonstration of immunogenicity with the poorly immunogenic B16 melanoma. Cancer Res. 43, 3507–3510 (1983).
  29. Zou, W., Wolchok, J. D. & Chen, L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci. Transl. Med. 8, 328rv324 (2016). · DOI
  30. Pitt Jonathan, M. et al. Resistance mechanisms to immune-checkpoint blockade in cancer: tumor-intrinsic and -extrinsic factors. Immunity 44, 1255–1269 (2016). · DOI
  31. Sagiv-Barfi, I. et al. Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK. Proc. Natl Acad. Sci. USA 112, E966–E972 (2015). · DOI
  32. Korpal, M. et al. Evasion of immunosurveillance by genomic alterations of PPARgamma/RXRalpha in bladder cancer. Nat. Commun. 8, 103 (2017). · DOI
  33. Tang, H. et al. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell. 29, 285–296 (2016). · DOI
  34. Johansson-Percival, A. et al. De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors. Nat. Immunol. 18, 1207–1217 (2017). · DOI
  35. Pfirschke, C. et al. Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy. Immunity 44, 343–354 (2016). · DOI
  36. Xu, J. et al. Near-infrared-triggered photodynamic therapy with multitasking upconversion nanoparticles in combination with checkpoint blockade for immunotherapy of colorectal cancer. ACS Nano 11, 4463–4474 (2017). · DOI
  37. He, C. et al. Core–shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy. Nat. Commun. 7, 12499 (2016). · DOI
  38. Deng, L. et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J. Clin. Invest. 124, 687–695 (2014). · DOI
  39. Min, Y. et al. Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy. Nat. Nanotechnol. 12, 877–882 (2017). · DOI
  40. Weber, J. S. et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 16, 375–384 (2015). · DOI
  41. Moslehi, J. J., Salem, J.-E., Sosman, J. A., Lebrun-Vignes, B. & Johnson, D. B. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. The Lancet 391, 933 (2018). · DOI · Paper page
  42. Lesterhuis, W. J. et al. A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients. Br. J. Cancer 103, 1415–1421 (2010). · DOI
  43. Banerjee, R., Tyagi, P., Li, S. & Huang, L. Anisamide-targeted stealth liposomes: a potent carrier for targeting doxorubicin to human prostate cancer cells. Int. J. Cancer 112, 693–700 (2004). · DOI
  44. Wang, Y. et al. Intravenous delivery of siRNA targeting CD47 effectively inhibits melanoma tumor growth and lung metastasis. Mol. Ther. 21, 1919–1929 (2013). · DOI

Cited by

Sorted by citations

See all 375

Metadata

Authors
Song, W., Shen, L., Wang, Y., Liu, Q., Goodwin, T. J., Li, J., Dorosheva, O., Liu, T., Liu, R., & Huang, L.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-06-08
Volume
9
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-018-04605-x
PMC
PMC5993831
Cited by
375
References
6
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Synergistic and low adverse effect cancer immunotherapy by immunogenic chemotherapy and locally expressed PD-L1 trap. https://app.cochat.ai/papers/10.1038/s41467-018-04605-x
The paper
Song, W., Shen, L., Wang, Y., Liu, Q., Goodwin, T. J., Li, J., Dorosheva, O., Liu, T., Liu, R., & Huang, L. (2018). Synergistic and low adverse effect cancer immunotherapy by immunogenic chemotherapy and locally expressed PD-L1 trap. Nature Communications. https://doi.org/10.1038/s41467-018-04605-x