Induction of systemic immune responses and reversion of immunosuppression in the tumor microenvironment by a therapeutic vaccine for cervical cancer

Che, Yuxin; Yang, Yang; Suo, Jinguo; An, Yujing; Wang, Xuelian

doi:10.1007/s00262-020-02651-3

Cited by 32 publications

(37 citation statements)

References 52 publications

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“…Single cell suspensions were prepared as described in our previous study. 21 The dissociated cells were dispersed in PBS (1×10 6 /mL) and stained for surface, intracellular and intranuclear molecules. Analysis was performed on a FACS Calibur flow cytometer (Becton Dickinson, USA) using FlowJo X software (Treestar, Ashland, OR, USA).…”

Section: Methodsmentioning

confidence: 99%

“…RT-PCR conditions were as follows: 95°C for 30 s, 95°C for 10 s, and 60°C for 30 s, for 40 cycles. All mouse-specific primers (Shenggong, Shanghai, China) for RT-PCR were described in our previous study 21 and are listed in Table 1 . β-actin was used as an endogenous control.…”

Section: Methodsmentioning

confidence: 99%

“…where for RT-PCR were described in our previous study 21 and are listed in Table 1. β-actin was used as an endogenous control.…”

Section: Assessment Of In Vivo Ctl Responsesmentioning

confidence: 99%

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<p>Mannose-Modified Liposome Co-Delivery of Human Papillomavirus Type 16 E7 Peptide and CpG Oligodeoxynucleotide Adjuvant Enhances Antitumor Activity Against Established Large TC-1 Grafted Tumors in Mice</p>

Zhao

Wang

Yang

et al. 2020

IJN

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Background: Previously, we demonstrated the therapeutic efficacy of a human papillomavirus (HPV) vaccine, including HPV16 E7 peptide and CpG oligodeoxynucleotides (CpG ODN), against small TC-1 grafted tumors. Here, we developed an HPV16 E7 peptide and CpG ODN vaccine delivered using liposomes modified with DC-targeting mannose, Lip E7/CpG, and determined its anti-tumor effects and influence on systemic immune responses and the tumor microenvironment (TME) in a mouse large TC-1 grafted tumor model. Methods: L-alpha-phosphatidyl choline (SPC), cholesterol (CHOL), 1,2-distearoyl-snglycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol-2000)] (DSPE-PEG-2000), 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and Mannose-PEG-DSPE, loaded with HPV16 E7 peptide and CpG ODN, were used to construct the Lip E7/CpG vaccine. The anti-tumor effects and potential mechanism of Lip E7/CpG were assessed by assays of tumor growth inhibition, immune cells, in vivo cytotoxic T lymphocyte (CTL) responses and cytokines, chemokines, CD31, Ki67 and p53 expression in the TME. In addition, toxicity of Lip E7/CpG to major organs was evaluated. Results: Lip E7/CpG had a diameter of 122.21±8.37 nm and remained stable at 4°C for 7 days. Co-delivery of HPV16 E7 peptide and CpG ODN by liposomes exerted potent antitumor effects in large (tumor volume ≥200mm 3) TC-1 grafted tumor-bearing mice with inhibition rates of 80% and 78% relative to the control and Free E7/CpG groups, respectively. Vaccination significantly increased numbers of CD4+ and CD8+ T cells, and IFN-γproducing cells in spleens and tumors and enhanced HPV-specific CTL responses, while reducing numbers of inhibitory cells including myeloid-derived suppressor cells and macrophages. Expression of cytokines and chemokines was altered and formation of tumor blood vessels was reduced in the Lip E7/CpG group, indicating possible modulation of the immunosuppressive TME to promote anti-tumor responses. Lip E7/CpG did not cause morphological changes in major organs. Conclusion: Lip E7/CpG induced anti-tumor effects by enhancing cellular immunity and improving tumor-associated immunosuppression. Mannose-modified liposomes are the promising vaccine delivery strategy for cancer immunotherapy.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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<p>Mannose-Modified Liposome Co-Delivery of Human Papillomavirus Type 16 E7 Peptide and CpG Oligodeoxynucleotide Adjuvant Enhances Antitumor Activity Against Established Large TC-1 Grafted Tumors in Mice</p>

Zhao

Wang

Yang

et al. 2020

IJN

Self Cite

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“…Although there are currently no licensed therapeutic HPV vaccines for cervical cancer, studies have validated that vaccines have both prophylactic and therapeutic effects on cervical cancer. Che et al 2020 [ 85 ] studied the HPV16 E7 43-77 peptide and the adjuvant unmethylated cytos 7ine-phosphate-guanosine oligodeoxynucleotide and demonstrated that this vaccine had substantial effects on systemic immune responses and the tumor microenvironment (TME) in a mouse model of cervical cancer. Their results indicated a significant increase in interferon (IFN)-γ-producing CD4 and CD8 T cells and tumor-infiltrating CD4 and CD8 T cells.…”

Section: Cancer Hallmarks Targetable By Innocuous Integrative Oncologymentioning

confidence: 99%

Biological Therapy with Complementary and Alternative Medicine in Innocuous Integrative Oncology: A Case of Cervical Cancer

Chizenga

Abrahamse

2021

Pharmaceutics

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Good medicine is based on good science, inquiry driven and open to new paradigms. For a complex disease such as cancer, a complex treatment regime that is well structured and multifactorial is indispensable. In the present day, Complementary and Alternative Medicine (CAM) therapies are being used frequently for cancer, alongside modern biological therapies and allopathic medicine, in what is called integrative oncology. In all conscience, the use of natural, less invasive interventions whenever possible is ideal. However, a comprehensive understanding of not only the etiopathology of individual cancers, but also the detailed genetic and epigenetic characteristics, the cancer hallmarks, that clearly show the blueprint of the cancer phenotype is a requisite. Different tumors have a common behavioral pattern, but their specific features at the genetic and epigenetic levels vary to a great extent. Henceforth, with so many failed attempts to therapy, drug formulations and combinations need a focused pre-assessment of the inherent features of individual cancers to destroy the tumors holistically by targeting these features. This review therefore presents innocuous therapeutic regimes by means of CAM and integrative medicine approaches that can specifically target the hallmarks of cancer, using the case of cervical cancer.

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“…Meanwhile, HPV mediates a variety of mechanisms to evade innate and adaptive immune responses, making the complex tumor microenvironment (TME) [ 13 ]. Based on limited evidence, some scholars believe that the immune status of local TME may play an important role in the relatively low response rate of HPV-related tumors [ 14 , 15 ]. Squamous cell carcinoma (SCC) is the most common histological subtype accounting for 75% of all cervical cancers [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of immune subtypes of cervical squamous cell carcinoma predicting prognosis and immunotherapy responses

Lü

Wang

et al. 2021

J Transl Med

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Background The main limitation of current immune checkpoint inhibitors (ICIs) in the treatment of cervical cancer comes from the fact that it benefits only a minority of patients. The study aims to develop a classification system to identify immune subtypes of cervical squamous cell carcinoma (SCC), thereby helping to screen candidates who may respond to ICIs. Methods A real-world cervical SCC cohort of 36 samples were analyzed. We used a nonnegative matrix factorization (NMF) algorithm to separate different expression patterns of immune-related genes (IRGs). The immune characteristics, potential immune biomarkers, and somatic mutations were compared. Two independent data sets containing 555 samples were used for validation. Results Two subtypes with different immunophenotypes were identified. Patients in sub1 showed favorable progression-free survival (PFS) and overall survival (OS) in the training and validation cohorts. The sub1 was remarkably related to increased immune cell abundance, more enriched immune activation pathways, and higher somatic mutation burden. Also, the sub1 group was more sensitive to ICIs, while patients in the sub2 group were more likely to fail to respond to ICIs but exhibited GPCR pathway activity. Finally, an 83-gene classifier was constructed for cervical SCC classification. Conclusion This study establishes a new classification to further understand the immunological diversity of cervical SCC, to assist in the selection of candidates for immunotherapy.

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Induction of systemic immune responses and reversion of immunosuppression in the tumor microenvironment by a therapeutic vaccine for cervical cancer

Cited by 32 publications

References 52 publications

<p>Mannose-Modified Liposome Co-Delivery of Human Papillomavirus Type 16 E7 Peptide and CpG Oligodeoxynucleotide Adjuvant Enhances Antitumor Activity Against Established Large TC-1 Grafted Tumors in Mice</p>

<p>Mannose-Modified Liposome Co-Delivery of Human Papillomavirus Type 16 E7 Peptide and CpG Oligodeoxynucleotide Adjuvant Enhances Antitumor Activity Against Established Large TC-1 Grafted Tumors in Mice</p>

Biological Therapy with Complementary and Alternative Medicine in Innocuous Integrative Oncology: A Case of Cervical Cancer

Identification of immune subtypes of cervical squamous cell carcinoma predicting prognosis and immunotherapy responses

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