PD-1/PD-L1 Inhibitors in Cervical Cancer

Liu, Yuncong; Wu, Li-Wha; Tong, Ruizhan; Yang, Feiyue; Yin, Lu; Li, Mengqian; You, Lei; Xue, Jianxin; Lü, You

doi:10.3389/fphar.2019.00065

Cited by 121 publications

(99 citation statements)

References 60 publications

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“…In recent years, immunotherapy has performed well in a variety of cancers including cervical cancer [25][26][27] . Blocking PD-L1 / PD-1 signaling pathway to attack tumor cells expressing PD-L1 is the current mainstream method 28 . Although the anticancer activity of PD-1 and PD-L1 inhibitors is exciting, such immunotherapy is not effective for all patients, and a meta-analysis shows that patients who receive PD-1 / PD-L1 inhibitors have a www.nature.com/scientificreports/ higher risk of rash, thyroid dysfunction, pruritus, pneumonia and colitis [29][30][31] .…”

Section: Discussionmentioning

confidence: 99%

29 immune-related genes pairs signature predict the prognosis of cervical cancer patients

Nie

et al. 2020

Sci Rep

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To screen the key immune genes in the development of cervical cancer, construct immune related gene pairs (IRGPs), and evaluate their influence on the prognosis of cervical cancer. Tumor Genome Atlas (TCGA) database and geo database were downloaded as training set and validation set respectively, and immune related gene data were downloaded from immport. IRGPs model is established by machine learning, and the model is analyzed and evaluated. Using the Uclcan to analyze the immune genes expression in cervical cancer, and to further explore the association with the expression level and the clinical stage and prognosis of cervical cancer. According to the analysis of training set, we identified 29 IRGPs as key gene pairs and constructed the model. The AUC value of the model was greater than 0.9, and the model group survival rate was conspicuous different (P < 0.001). The reliability of the model was confirmed in the validation group. Our IRGPs play an important role in the occurrence and development of cervical cancer, and can be used as a prognostic marker and potential new target of cervical cancer. Cervical cancer is one of the four most common gynecological tumors 1. Every year, at least 569,847 women in the world are diagnosed with cervical cancer, and more than 311,365 people are killed 2. In recent years, the incidence rate of cervical cancer has decreased significantly through universal screening and health knowledge. However, the incidence rate of cervical cancer is still high in developing countries 3. For women with low education in less developed areas, the coverage rate of cervical cancer screening is still very low 4. Squamous cell carcinoma is the most common type of cervical cancer, accounting for 75% of cervical cancer cases, while adenocarcinoma only accounts for about 20%. In developing countries, 70% of cervical cancer patients have local infiltration or metastasis, which has led to the high mortality of cervical cancer in developing countries. Early cervical cancer is usually treated by radical hysterectomy. When there are risk factors such as lymph node metastasis and endometriosis that may lead to recurrence, they will be treated with chemotherapy 5. The standard treatment for patients with locally advanced cervical cancer is conventional radiation therapy(CRT) 6. The five-year survival rate of patients with locally advanced cervical cancer can be as high as 75-85% after surgical resection, radiotherapy, chemotherapy, CRT, and so on 7. However, at present, all treatment methods are not effective for patients with paraaortic lymph node metastasis, and their three-year progression free survival time (PFS) and total survival time (OS) are 34% and 39% 8,9 , respectively. The five-year survival rate of cervical cancer patients with recurrence and metastasis was as low as 15%. Limited treatment is the main reason for this situation. Now, palliative chemotherapy is the most commonly used for patients with metastatic and recurrent cervical cancer 10. The median survival time of patients with metastati...

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Section: Discussionmentioning

confidence: 99%

29 immune-related genes pairs signature predict the prognosis of cervical cancer patients

Nie

et al. 2020

Sci Rep

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“…PD-1 blockade therapy has recently been approved for the treatment of recurrent or metastatic HNSCC and advanced cervical cancers. [7][8][9] Using an OVA-expressing tumor model, it has previously been demonstrated that the antitumor effect by replicating LCMV vectors, from which TT1-E7E6 is designed, is dependent on CD8 + T cells. 19 Here, we sought to evaluate whether the antitumor efficacy of TT1-E7E6 can be enhanced with concomitant anti-PD-1 therapy.…”

Section: Tt1-e7e6 In Combination With Pd-1 Checkpoint Inhibitor Theramentioning

confidence: 99%

“…[4][5][6] In recent years, ICI targeting programmed cell death 1 (PD-1) or its ligand PD-L1 have been approved for the treatment of recurrent or metastatic HNSCC as well as advanced cervical cancers. [7][8][9] Therapeutic HPV vaccines aiming to induce antitumor CTL responses are emerging as a promising strategy to treat HPVpositive cancers, especially when combined with ICI. 10 The HPV oncoproteins E6 and E7 commonly targeted by these therapeutic vaccines are expressed in all HPV-infected cells; persist throughout the viral life cycle and drive the transformation of healthy cells into cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Live-attenuated lymphocytic choriomeningitis virus-based vaccines for active immunotherapy of HPV16-positive cancer

Schmidt¹,

Bonilla

Reiter³

et al. 2020

OncoImmunology

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Infection with human papillomavirus (HPV) is associated with a variety of cancer types and limited therapy options. Therapeutic cancer vaccines targeting the HPV16 oncoproteins E6 and E7 have recently been extensively explored as a promising immunotherapy approach to drive durable antitumor T cell immunity and induce effective tumor control. With the goal to achieve potent and lasting antitumor T cell responses, we generated a novel lymphocytic choriomeningitis virus (LCMV)-based vaccine, TT1-E7E6, targeting HPV16 E6 and E7. This replication-competent vector was stably attenuated using a three-segmented viral genome packaging strategy. Compared to wild-type LCMV, TT1-E7E6 demonstrated significantly reduced viremia and CNS immunopathology. Intravenous vaccination of mice with TT1-E7E6 induced robust expansion of HPV16specific CD8 + T cells producing IFN-γ, TNF-α and IL-2. In the HPV16 E6 and E7-expressing TC-1 tumor model, mice immunized with TT1-E7E6 showed significantly delayed tumor growth or complete tumor clearance accompanied with prolonged survival. Tumor control by TT1-E7E6 was also achieved in established largesized tumors in this model. Furthermore, a combination of TT1-E7E6 with anti-PD-1 therapy led to enhanced antitumor efficacy with complete tumor regression in the majority of tumor-bearing mice that were resistant to anti-PD-1 treatment alone. TT1-E7E6 vector itself did not exhibit oncolytic properties in TC-1 cells, while the antitumor effect was associated with the accumulation of HPV16-specific CD8 + T cells with reduced PD-1 expression in the tumor tissues. Together, our results suggest that TT1-E7E6 is a promising therapeutic vaccine for HPV-positive cancers.

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“…1 Although the incidence of cervical cancer has been greatly reduced by the use of Human Papilloma Virus (HPV) vaccines and cervical cancer screening, the prevalence of cervical cancer has increased in developing countries. 2,3 For cervical cancer, traditional treatments include surgery, medication, and radiation therapy. Although a great deal of progress has been made, there are limitations with traditional treatments: surgery is invasive and risky, chemotherapy has many side effects, drugs have toxicity, and systemic adverse reactions have greatly reduced the quality of life of patients.…”

Section: Introductionmentioning

confidence: 99%

<p>Ultrasound-Mediated Co-Delivery of miR-34a and sPD-1 Complexed with Microbubbles for Synergistic Cancer Therapy</p>

Qin

Tang

et al. 2020

CMAR

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Background: miR-34a was downregulated and PD-L1 was upregulated in cervical cancer; however, the treatment of cervical cancer lacks precision and targeting. This study explored the ultrasound-mediated co-delivery of miR-34a and sPD-1 complexes with microbubbles for synergistic cancer therapy. Methods: Cationic lipid microbubbles (CLMBs) were prepared by membrane hydration and mechanical oscillation. U14 subcutaneous xenograft mice were injected with CLMBs-loaded sPD-1 and miR-34a combined with ultrasound targeted destruction, and tumor volume and tumor weight of mice were measured. TUNEL apoptosis test and the mRNA expression of apoptosis-related gene Bcl-2 and Bax were analyzed by qRT-PCR. Antitumor immunerelated cytokines IFN-γ were investigated by qRT-PCR, LDH Cytotoxicity Assay Kit were performed to test cytotoxic T lymphocytes (CTL). Results: CLMBs were successfully prepared and the plasmid bound to its surface. The tumor volume and weight were specifically decreased by ultrasound-mediated co-delivery of miR-34a and sPD-1 complexes with microbubbles, apoptosis was induced and the apoptosis suppressor gene Bcl-2 was downregulated and proapoptotic gene Bax were upregulated. qRT-PCR analysis revealed that antitumor immunity-related IFN-γ was strongly upregulated in mice, which were treated with CLMBs-loaded sPD-1 and miR-34a combined with ultrasound targeted destruction, and the percentage of CTL was increased. Conclusion: These findings from the study demonstrated that CLMBs could deliver miR-34a and sPD-1, combined with ultrasound targeted destruction, could suppress the tumor tissue growing, induce apoptosis and enhance antitumor immunity in U14 subcutaneous xenograft mice.

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PD-1/PD-L1 Inhibitors in Cervical Cancer

Cited by 121 publications

References 60 publications

29 immune-related genes pairs signature predict the prognosis of cervical cancer patients

29 immune-related genes pairs signature predict the prognosis of cervical cancer patients

Live-attenuated lymphocytic choriomeningitis virus-based vaccines for active immunotherapy of HPV16-positive cancer

<p>Ultrasound-Mediated Co-Delivery of miR-34a and sPD-1 Complexed with Microbubbles for Synergistic Cancer Therapy</p>

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