Patterns and genomic correlates of PD-L1 expression in patients with biliary tract cancers

Mody, Kabir; Starr, Jason S.; Saul, Michelle; Poorman, Kelsey; Weinberg, Benjamin A.; Salem, Mohamed E.; Vanderwalde, Ari M.; Shields, Anthony F.

doi:10.21037/jgo.2019.08.08

Cited by 54 publications

(49 citation statements)

References 29 publications

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“…Immunooncology has become a promising approach in the field of new anticancer drug development [ 35 , 36 ]. PD-L1 and HHLA2 are potential immunotherapeutic targets for iCCA patients [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Systemic Immune-Inflammation Index Is a Prognostic Predictor in Patients with Intrahepatic Cholangiocarcinoma Undergoing Liver Transplantation

Ren

Cheng

et al. 2021

Mediators of Inflammation

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Background. It was reported that systemic immune inflammation index (SII) was related to poor prognosis in a variety of cancers. We aimed to investigate the ability of the prognostic predictors of SII in patients with intrahepatic cholangiocarcinoma (iCCA) undergoing liver transplantation (LT). Methods. The 28 iCCA patients who underwent LT at our hospital between 2013 and 2018 were reviewed. Kaplan–Meier survival curves and Cox regression analyses were used to evaluate the prognostic significance of SII. Patients were divided into the high and low SII groups according to the cut-off value. Results. The 1-, 3-, and 5-year OS rates were significantly lower in the high SII group (85.7%, 28.6%, and 21.4%, respectively) than in the low SII group (92.9%, 71.4%, and 57.2%, respectively; P = 0.009 ). The 1-, 3-, and 5-year RFS rates were, respectively, 57.1%, 32.7%, and 21.8% in the high SII group and 85.7%, 61.1%, and 61.1% in the low SII group ( P = 0.021 ). SII ≥ 447.48 × 10 9/L (HR 0.273, 95% CI 0.082–0.908; P = 0.034 ) was an independent prognostic factor for OS. Conclusions. Our results showed that SII can be used to predict the survival of patients with iCCA who undergo LT.

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Section: Discussionmentioning

confidence: 99%

Systemic Immune-Inflammation Index Is a Prognostic Predictor in Patients with Intrahepatic Cholangiocarcinoma Undergoing Liver Transplantation

Ren

Cheng

et al. 2021

Mediators of Inflammation

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“…Mutation of ARID1A and CREBBP may be poor prognostic factors for follicular lymphoma receiving immunochemotherapy ( 32 ). Genomic alteration frequency of ring finger protein 43 (RNF43) are higher in PD-L1-positive patients with biliary tract cancer (BTC) compared with PD-L1-negative patients, which suggest that mutation status of RNF43 may be a poor prognostic factor for BTC receiving immunotherapy ( 33 ). Treg cell expansion requires Notch3 signaling, which imply that the mutation status of Notch3 may affect the function of Treg cells ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Somatic mutations in genes associated with mismatch repair predict survival in patients with metastatic cancer receiving immune checkpoint inhibitors

et al. 2020

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Immune checkpoint inhibitors (ICIs) have emerged as one of the most promising therapeutic options for patients with advanced cancer. The aim of the present study was to investigate the prognostic value of somatic mutations in mismatch repair (MMR) genes in metastatic cancers after ICI treatment, as well as their association with tumor mutational burden (TMB). Information regarding gene mutations in mismatch repair and the survival time of patients with advanced cancer following ICI treatment was collected from the cBioPortal database. The prognostic value of somatic mutations in MMR genes and the association between the mutation status and TMB score were analyzed among multiple types of cancer. Somatic mutation frequency in the MMR genes was identified to be 7% among all patients, which varied across different types of cancer. Somatic mutations in the MMR genes were associated with improved overall survival time in all tested patients (P=0.004). Following stratification by type of ICI treatment, a significant association was observed between somatic mutations in the MMR genes and overall survival time in patients treated with cytotoxic T-lymphocyte-associated protein 4 inhibitors (P= 0.01). In addition, marked but non-significant association between somatic mutations in the MMR genes and overall survival time was revealed in patients administered with programmed death-1/programmed death-ligand-1 inhibitors (P=0.09). Multivariate Cox proportional hazards regression analysis demonstrated that somatic mutations in MMR genes were significantly associated with overall survival time (hazard ratio, 0.683; 95% confidence interval, 0.497-0.938; P=0.01). Patients with somatic mutations in the MMR genes demonstrated higher TMB compared with those not harboring mutations (P<0.01). The results of the present study suggested that somatic mutations in the MMR genes may be used as a prognostic marker of a positive outcome in patients with metastatic cancer receiving ICI treatment, since somatic mutations in the MMR genes may be one of the main factors affecting the tumor mutation load.

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“…236,237 Specifically, PD-L1 expression in GBC (23%) was comparable to breast cancer (23%), urothelial cancer (20%), and pulmonary squamous cell carcinoma (27%). 238,239 Mody et al 240 found that 12% patients with tumor cell-expressing PD-L1 and 55% patients with tumor-infiltrating lymphocyte (TIL)-expressing PD-1 in a total of 203 GBC patients were associated with corresponding genetic aberrations and tumor mutational burden (TMB) status. Likewise, Lin et al 241 showed that 18% of 66 GBC patients were positive for PD-L1 expressed by tumor cells.…”

Section: Pd-1/pd-l1mentioning

confidence: 99%

Overview of current targeted therapy in gallbladder cancer

Song

et al. 2020

Sig Transduct Target Ther

111

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Gallbladder cancer (GBC) is rare, but is the most malignant type of biliary tract tumor. Unfortunately, only a small population of cancer patients is acceptable for the surgical resection, the current effective regimen; thus, the high mortality rate has been static for decades. To substantially circumvent the stagnant scenario, a number of therapeutic approaches owing to the creation of advanced technologic measures (e.g., next-generation sequencing, transcriptomics, proteomics) have been intensively innovated, which include targeted therapy, immunotherapy, and nanoparticle-based delivery systems. In the current review, we primarily focus on the targeted therapy capable of specifically inhibiting individual key molecules that govern aberrant signaling cascades in GBC. Global clinical trials of targeted therapy in GBC are updated and may offer great value for novel pathologic and therapeutic insights of this deadly disease, ultimately improving the efficacy of treatment.

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Patterns and genomic correlates of PD-L1 expression in patients with biliary tract cancers

Cited by 54 publications

References 29 publications

Systemic Immune-Inflammation Index Is a Prognostic Predictor in Patients with Intrahepatic Cholangiocarcinoma Undergoing Liver Transplantation

Systemic Immune-Inflammation Index Is a Prognostic Predictor in Patients with Intrahepatic Cholangiocarcinoma Undergoing Liver Transplantation

Somatic mutations in genes associated with mismatch repair predict survival in patients with metastatic cancer receiving immune checkpoint inhibitors

Overview of current targeted therapy in gallbladder cancer

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