Immune Checkpoint Inhibitors in Gynecological Cancers: Update of Literature and Perspectives of Clinical Research

doi:10.21873/anticanres.12042

Cited by 33 publications

(18 citation statements)

References 87 publications

(111 reference statements)

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“…Although the median TMB in cervical cancer cases was not high, moderate to high TMB values were observed in a subset of patients (28.13%), which may be a potential group that can benefit from immune checkpoint inhibitor therapy. Several ongoing trials are investigating immune checkpoint inhibitors alone or in combination with chemotherapy or other biological agents in patients with advanced and recurrent cervical cancer, but the results have not been published yet 32 .…”

Section: Discussionmentioning

confidence: 99%

Molecular profiles and tumor mutational burden analysis in Chinese patients with gynecologic cancers

Wang

Fan

et al. 2018

Sci Rep

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The goal of this work was to investigate the tumor mutational burden (TMB) in Chinese patients with gynecologic cancer. In total, 117 patients with gynecologic cancers were included in this study. Both tumor DNA and paired blood cell genomic DNA were isolated from formalin-fixed paraffin-embedded (FFPE) specimens and blood samples, and next-generation sequencing was performed to identify somatic mutations. TP53, PTEN, ARID1A, and PIK3CA alterations were significantly different in various types of gynecologic cancers (p = 0.001, 1.15E-07, 0.004, and 0.009, respectively). The median TMB of all 117 gynecologic tumor specimens was 0.37 mutations/Mb, with a range of 0–41.45 mutations/Mb. Despite the lack of significant difference, endometrial cancer cases had a higher median TMB than cervical and ovarian cancer cases. Younger gynecologic cancer patients (age <40 years) had a significantly lower TMB than older patients (age ≥40 years) (p = 0.04). In addition, TMB was significantly increased with increasing clinical stage of disease (p = 0.001). PTEN alterations were commonly observed in patients with a moderate to high TMB (n = 8, 38.10%, p = 9.95E-04). Although limited by sample size, all of the patients with TSC2 (n = 3, p = 3.83E-11) or POLE (n = 2, p = 0.005) mutations had a moderate to high TMB. Further large-scale, prospective studies are needed to validate our findings.

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Section: Discussionmentioning

confidence: 99%

Molecular profiles and tumor mutational burden analysis in Chinese patients with gynecologic cancers

Wang

Fan

et al. 2018

Sci Rep

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“…Taking into account that many primary USCC cases exhibit abnormal p53 expression, it seems reasonable that mutant p53 may be an attractive target for therapy in drug form [30]. Due to PD-1 and PD-1 expression in cervical cancer tissues, immune check-point inhibitors, as nivolumab, pembrolizumab, ipilimumab, or even antiangiogenic drug, bevacizumab, may have an important role in maintenance therapy in patients with the recurrent, metastatic or persistent disease after CHTH [38]. The management of this disease underlines the need for accumulating experience through case reports, due to its extreme rarity.…”

Section: Discussionmentioning

confidence: 99%

Serous Carcinoma of the Uterine Cervix, an Extremely Rare Aggressive Entity: A Literature Review

Jońska-Gmyrek

Żółciak-Siwińska

Gmyrek³

et al. 2018

Gynecol Obstet Invest

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Background/Aims: Serous carcinoma of the uterine cervix (USCC) is an extremely rare subtype. To establish the treatment strategy in patients with USCC is an important issue. Methods: MEDLINE (PubMed) was searched for all articles published after the first publication by Lurie et al. [Eur J Obstet Gynecol Reprod Biol 1991; 40: 79–81], reporting woman diagnosed with USCC. Because of limited numbers of studies on the topic of the study, we could not keep a restriction of eliminating smaller sample sizes. Results: A search of PubMed demonstrated that 113 cases of USCC have been reported in the literature since the first publication. The current treatment modality adopted for early cervical cancer is hysterectomy with bilateral iliac-obturator lymphadenectomy and postoperative radiotherapy (RT) or radiochemotherapy (RT-CT) if risk factors for cervical carcinoma appear. The treatment strategy for locally advanced USCC is preoperative RT-CT or chemotherapy (CHTH) with the intention to treat the patient surgically. The treatment option for disseminated disease is CHTH with paclitaxel and carboplatin. Conclusion: Risk factors and a more advanced clinical stage of USCC have an impact on poor outcomes despite the use of standard treatment methods, adapted for cervical cancer. The outside-pelvic failures tend to seek effective systemic treatment.

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“…Boichard A et al found that Kataegis and APOBEC3 overexpression participated in regulation of PD-L1 expression [ 83 ]. Furthermore, polymerase δ1 ( POLD1 ) and polymerase ε ( POLE ) variations lead to extremely high frequency of somatic mutation which affects tumor immunogenicity [ 84 , 85 ].…”

Section: Oncogenic Driver Mutations and Other Mutationsmentioning

confidence: 99%

Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

et al. 2018

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Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) is a negative modulatory signaling pathway for activation of T cell. It is acknowledged that PD-1/PD-L1 axis plays a crucial role in the progression of tumor by altering status of immune surveillance. As one of the most promising immune therapy strategies, PD-1/PD-L1 inhibitor is a breakthrough for the therapy of some refractory tumors. However, response rate of PD-1/PD-L1 inhibitors in overall patients is unsatisfactory, which limits the application in clinical practice. Therefore, biomarkers which could effectively predict the efficacy of PD-1/PD-L1 inhibitors are crucial for patient selection. Biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, density of tumor infiltrating lymphocyte (TIL), tumor mutational burden, and mismatch-repair (MMR) deficiency, have been noticed to associate with treatment effect of anti-PD-1/anti-PD-L1 therapy. Furthermore, gut microbiota, circulating biomarkers, and patient previous history have been found as valuable predictors as well. Therefore establishing a comprehensive assessment framework involving multiple biomarkers would be meaningful to interrogate tumor immune landscape and select sensitive patients.

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Immune Checkpoint Inhibitors in Gynecological Cancers: Update of Literature and Perspectives of Clinical Research

Cited by 33 publications

References 87 publications

Molecular profiles and tumor mutational burden analysis in Chinese patients with gynecologic cancers

Molecular profiles and tumor mutational burden analysis in Chinese patients with gynecologic cancers

Serous Carcinoma of the Uterine Cervix, an Extremely Rare Aggressive Entity: A Literature Review

Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

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