The Role of Biomarkers for the Prediction of Response to Checkpoint Immunotherapy and the Rationale for the Use of Checkpoint Immunotherapy in Cervical Cancer

Otter, Sophie; Chatterjee, Jayanta; Stewart, Alexandra J.; Michael, Agnieszka

doi:10.1016/j.clon.2019.07.003

Cited by 61 publications

(38 citation statements)

References 77 publications

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“…The standard treatment for recurrent or metastatic cervical cancer is a combination of chemotherapy and bevacizumab ( 159 – 162 ), but treatment options for recurrent disease are limited. Almost all cervical cancers are mediated by human papillomavirus infection which, when considered alongside relatively high mutation burden and expression of PD-L1, makes immunotherapy a potentially attractive treatment strategy ( 163 , 164 ).…”

Section: Anti-vegf As Immunotherapy: Evidence From Clinical Trialsmentioning

confidence: 99%

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

Hack¹,

Zhu

Wang³

2020

Front. Immunol.

167

132

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Section: Anti-vegf As Immunotherapy: Evidence From Clinical Trialsmentioning

confidence: 99%

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

Hack¹,

Zhu

Wang³

2020

Front. Immunol.

167

132

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“…Almost all cases of uterine cervical cancer are caused by high-risk human papillomavirus (HPV) infection [ 25 ] and HPV expresses foreign antigens within host cells. Although immunotherapy has the potential to improve the survival of uterine cervical cancer patients, the response rate of uterine cervical cancer to checkpoint immunotherapy is 10–25% [ 26 ]. Previous studies suggest the differences in the immunological microenvironments and escape mechanisms by histological subtypes.…”

Section: Discussionmentioning

confidence: 99%

Induction of Micronuclei in Cervical Cancer Treated with Radiotherapy

Kobayashi¹,

Oike

Murata

et al. 2020

JPM

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Micronuclei (MN) trigger antitumor immune responses via the cyclic GMP-AMP synthase-signaling effector stimulator of interferon genes (cGAS-STING) pathway. Radiotherapy induces MN in peripheral blood lymphocytes. However, data for solid tumors are lacking. Here, we analyzed MN post-radiotherapy in solid tumor samples. Tumor biopsy specimens were obtained from seven prospectively recruited patients with cervical cancer, before treatment and after receiving radiotherapy at a dose of 10 Gy (in five fractions). The samples were stained with 4′,6-diamidino-2-phenylindole dihydrochloride, and 200 nuclei per sample were randomly identified and assessed for the presence of MN or apoptosis, based on nuclear morphology. The median number of MN-harboring nuclei was significantly greater in samples from patients treated with radiotherapy than in pre-treatment samples (151 (range, 16–327) versus 28 (range, 0–61); p = 0.015). No significant differences in the number of apoptotic nuclei were observed between pre-treatment and 10 Gy samples (5 (range, 0–30) versus 12 (range, 2–30); p = 0.30). This is the first report to demonstrate MN induction by radiotherapy in solid tumors. The results provide clinical evidence of the activation of antitumor immune responses by radiotherapy.

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“…In addition, several immune checkpoint biomarkers and cytokines have been identified to mediate the crosstalk between cancer cells and stromal microenvironment (De Nola et al 2019;Otter et al 2019). In the last decade, various studies have investigated the relationship between the prognosis of patients with primary CSCC and the immunological landscape through highthroughput quantitative measurements of cellular and molecular characteristics (Minion & Tewari 2018;Punt et al 2015).…”

Section: Manuscript To Be Reviewedmentioning

confidence: 99%

Peer Review #1 of "Mining of prognosis-related genes in cervical squamous cell carcinoma immune microenvironment (v0.1)"

2020

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The aim of this study was to explore the effective immune scoring method and mine the novel and potential immune microenvironment-related diagnostic and prognostic markers for cervical squamous cell carcinoma (CSSC). Materials and Methods: The Cancer Genome Atlas (TCGA) data was downloaded and multiple data analysis approaches were initially used to search for the immune-related scoring system on the basis of Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm. After-wards, the representative genes in the gene modules correlated with immune-related scores based on ESTIMATE algorithm were further screened using Weighted Gene Co-expression Network Analysis (WGCNA) and network topology analysis. Gene functions were mined through enrichment analysis, followed by exploration of the correlation between these genes and immune checkpoint genes. Finally, survival analysis was applied to search for genes with significant association with overall survival and external database was employed for further validation. Results: The immune-related scores based on ESTIMATE algorithm was closely associated with other categories of scores, the HPV infection status, prognosis and the mutation levels of multiple CSCC-related genes (HLA and TP53). 18 new representative immune microenvironment-related genes were finally screened closely associated with patient prognosis and were further validated by the independent dataset GSE44001. Conclusion: Our present study suggested that the immune-related scores based on ESTIMATE algorithm can help to screen out novel immune-related diagnostic indicators, therapeutic targets and prognostic predictors in CSCC.

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The Role of Biomarkers for the Prediction of Response to Checkpoint Immunotherapy and the Rationale for the Use of Checkpoint Immunotherapy in Cervical Cancer

Cited by 61 publications

References 77 publications

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

Induction of Micronuclei in Cervical Cancer Treated with Radiotherapy

Peer Review #1 of "Mining of prognosis-related genes in cervical squamous cell carcinoma immune microenvironment (v0.1)"

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