Biomarkers for predicting the efficacy of immune checkpoint inhibitors

Wang, Chengji; Wang, He-nan; Wang, Liang

doi:10.7150/jca.65012

Cited by 17 publications

(13 citation statements)

References 165 publications

(172 reference statements)

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“…Additionally, contraindications are based on observations of toxicity risk or tumor hyperprogression. The most common contraindications relevant to lung cancer therapy have been classic activating mutations in EGFR, where prior TKI use has been linked to a long-lasting increased risk of severe and almost always fatal pneumonitis, requiring permanent discontinuation of immunotherapy, with the risk increasing with additionally therapeutic modalities such as radiotherapy [ 80 , 81 ]). Importantly, MDM2 amplification in solid tumors has been associated with the paradoxical tumor hyper-progression seen in patients who receive PD-1/PD-L1 checkpoint blockade [ 82 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies?

Ullah

Pulliam

Karki

et al. 2022

Clinics and Practice

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Programmed death-ligand (PD-L) 1 and 2 are ligands of programmed cell death 1 (PD-1) receptor. They are members of the B7/CD28 ligand-receptor family and the most investigated inhibitory immune checkpoints at present. PD-L1 is the main effector in PD-1-reliant immunosuppression, as the PD-1/PD-L pathway is a key regulator for T-cell activation. Activation of T-cells warrants the upregulation of PD-1 and production of cytokines which also upregulate PD-L1 expression, creating a positive feedback mechanism that has an important role in the prevention of tissue destruction and development of autoimmunity. In the context of inadequate immune response, the prolonged antigen stimulation leads to chronic PD-1 upregulation and T-cell exhaustion. In lung cancer patients, PD-L1 expression levels have been of special interest since patients with non-small cell lung cancer (NSCLC) demonstrate higher levels of expression and tend to respond more favorably to the evolving PD-1 and PD-L1 inhibitors. The Food and Drug Administration (FDA) has approved the PD-1 inhibitor, pembrolizumab, alone as front-line single-agent therapy instead of chemotherapy in patients with NSCLC and PD-L1 ≥1% expression and chemoimmunotherapy regimens are available for lower stage disease. The National Comprehensive Cancer Network (NCCN) guidelines also delineate treatment by low and high expression of PD-L1 in NSCLC. Thus, studying PD-L1 overexpression levels in the different histological subtypes of lung cancer can affect our approach to treating these patients. There is an evolving role of immunotherapy in the other sub-types of lung cancer, especially small cell lung cancer (SCLC). In addition, within the NSCLC category, squamous cell carcinomas and non-G12C KRAS mutant NSCLC have no specific targetable therapies to date. Therefore, assessment of the PD-L1 expression level among these subtypes of lung cancer is required, since lung cancer is one of the few malignances wherein PD-L1 expression levels is so crucial in determining the role of immunotherapy. In this study, we compared PD-L1 expression in lung cancer according to the histological subtype of the tumor.

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Section: Discussionmentioning

confidence: 99%

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies?

Ullah

Pulliam

Karki

et al. 2022

Clinics and Practice

View full text Add to dashboard Cite

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“…Such important factors are tumor-infiltrating lymphocytes, complex myeloid cells, lipid-associated macrophages, cancer-associated fibroblasts ( CAFs ), and other molecules that promote the growth and migration of tumor cells [ 99 ]. Tumor-infiltrating lymphocytes ( TIL ) are considered an important prognostic factor in various types of oncological diseases [ 100 , 101 , 102 , 103 , 104 ] including triple-negative breast cancer ( TNBC ) [ 105 , 106 ]. In general, tumor-infiltrating lymphocytes are strong indicators of tumor immunogenicity [ 107 ]; however, as a heterogeneous population, TILs are associated both with positive and negative outcomes.…”

Section: Tumor Microenvironment Tumor Infiltrating Lymphocytes ( ...mentioning

confidence: 99%

Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer

Kudelova

Smolár

Holubeková

et al. 2022

IJMS

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Heterogeneity of triple-negative breast cancer is well known at clinical, histopathological, and molecular levels. Genomic instability and greater mutation rates, which may result in the creation of neoantigens and enhanced immunogenicity, are additional characteristics of this breast cancer type. Clinical outcome is poor due to early age of onset, high metastatic potential, and increased likelihood of distant recurrence. Consequently, efforts to elucidate molecular mechanisms of breast cancer development, progression, and metastatic spread have been initiated to improve treatment options and improve outcomes for these patients. The extremely complex and heterogeneous tumor immune microenvironment is made up of several cell types and commonly possesses disorganized gene expression. Altered signaling pathways are mainly associated with mutated genes including p53, PIK3CA, and MAPK, and which are positively correlated with genes regulating immune response. Of note, particular immunity-associated genes could be used in prognostic indexes to assess the most effective management. Recent findings highlight the fact that long non-coding RNAs also play an important role in shaping tumor microenvironment formation, and can mediate tumor immune evasion. Identification of molecular signatures, through the use of multi-omics approaches, and effector pathways that drive early stages of the carcinogenic process are important steps in developing new strategies for targeted cancer treatment and prevention. Advances in immunotherapy by remodeling the host immune system to eradicate tumor cells have great promise to lead to novel therapeutic strategies. Current research is focused on combining immune checkpoint inhibition with chemotherapy, PARP inhibitors, cancer vaccines, or natural killer cell therapy. Targeted therapies may improve therapeutic response, eliminate therapeutic resistance, and improve overall patient survival. In the future, these evolving advancements should be implemented for personalized medicine and state-of-art management of cancer patients.

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“…Accordingly, there is an urgent need for additional research on new molecular markers that can predict the efficacy of pembrolizumab in patients with advanced BTC. Further studies are needed on peripheral blood cell biomarkers, such as the circulating tumor DNA, peripheral immune cells, peripheral cytokines, peripheral blood T-cell receptors, lactate dehydrogenase, interleukin-8, and soluble PD-L1, to determine the immune checkpoint inhibitor efficacy [ 23 , 24 ]. Many studies report that the biliary tract originates from the primitive gut and has a very similar morphology, particularly in the extrahepatic tract, and many researchers have demonstrated that DCLK1 (Doublecortin-like kinase 1) is a cancer stem cell marker in the intestinal tum [ 25 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Factors in Patients Treated with Pembrolizumab as a Second-Line Treatment for Advanced Biliary Tract Cancer

Park

Sung

Kim

et al. 2022

Cancers

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Some BTC types respond to pembrolizumab, but there are no known prognostic factors to predict its treatment benefits. In this study, we attempted to identify the prognostic factors associated with pembrolizumab as a second-line treatment for gemcitabine-refractory BTC. This retrospective and single tertiary-center study involved all the consecutive patients (n = 80) with refractory advanced BTC, who were diagnosed as programmed cell death ligand 1-positive and treated with pembrolizumab between August 2017 and February 2021. The overall survival (OS) was analyzed using Cox regression analysis. The median OS was 6.0 months [95% confidence interval (CI): 3.87–8.20]; median progression-free survival was 1.9 months (95% CI: 1.82–1.98); and the response rate was 15.9%. In the multivariate Cox regression analysis, the TB [adjusted hazard ratio (HR) = 2.286; 95% CI: 1.177–4.440; p = 0.015), albumin levels (adjusted HR = 0.392; 95% CI: 0.211–0.725; p = 0.003), ALP levels (adjusted HR = 1.938; 95% CI: 1.105–3.400; p = 0.021), and LMR (adjusted HR = 0.325; 95% CI: 0.173–0.609; p < 0.001) were identified as significant variables associated with the OS. High albumin levels and LMR and low ALP levels and TB were significantly associated with better OS in patients treated with pembrolizumab.

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Biomarkers for predicting the efficacy of immune checkpoint inhibitors

Cited by 17 publications

References 165 publications

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies?

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies?

Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer

Prognostic Factors in Patients Treated with Pembrolizumab as a Second-Line Treatment for Advanced Biliary Tract Cancer

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