TMB + PD-L1 expression

This review will provide an overview of the components of the RCC tumor microenvironment and discuss their role in disease progression and resistance to ICI. We will then highlight the current and future ICI predictive biomarkers assessed in mccRCC with a major focus on immunohistochemistry markers and genomic signatures.

Atezolizumab, when added to carboplatin and etoposide, improved both progression-free survival and overall survival. Biomarker development has stalled as PD-L1 expression and tumor mutational burden have not been useful predictive biomarkers. However, based on the significant survival improvements, both atezolizumab and durvalumab were approved by the US Food and Drug Administration to be given with first-line chemotherapy, and these regimens represent the new standards of care for SCLC.

This study indicates that coexisting alterations in a limited set of genes characterize a subset of LUAD unresponsive to immunotherapy and with high TMB. An immune-cold microenvironment may account for the clinical course of the disease.

In the validation cohort, the immunotherapy efficacy of patients with KDM5C mutations was better than that of KDM5C wild-type patients, with median overall survival 21 months (95% CI, 12.4 to 29.6) and 11 months (95% CI, 8.9 to 13.1) (hazard ratio for death, 0.63; 95% CI, 0.26 to 1.53). Conclusion KDM5C mutations are associated to better efficacy of immunotherapy and have potential value for guiding clinical practice.

BRCA and PALB2 mutations were found in a significant subgroup of PDACs. These mutations were associated with a distinct molecular profile potentially predictive for response to immune-checkpoint inhibitor therapy. Therefore, these data provide a rationale to evaluate PARP inhibitors in combination with immune-checkpoint inhibitors in patients with BRCA/PALB2-mutated PDAC.

A deeper understanding of the underlying biological mechanisms of acquired resistance to ICIs is helpful to overcome these obstacles. In this review, we describe the cutting-edge progress made in patients with lung cancer, the optimal duration of ICI treatment, ICIs in some special populations, the unique response patterns during ICI treatment, the emerging predictive biomarkers, and our understanding of primary and acquired resistance mechanisms to ICI treatment.

Our study has identified that TP53 confers worse survival and response to platinum chemotherapy compared to BAP1. Overall PDL1 expression and TMB is low in patients with MPM resulting in limited benefit from single agent PD-1/PD-L1 agent.

From these biomarkers, peripheral blood-based biomarkers are promising options for the prediction of immunotherapy efficacy with ease of access, repeatability and low cost. This review provides an overview of recent developments on the biomarkers in immunotherapy efficacy together with comments on future perspectives.

Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherapeutic agents provide opportunities to enhance the immune response to prostate tumors.

ICIs could be considered to treat patients whose NSCLCs harbor a METex14 mutation. More biological marker data are needed to identify which patients are most likely to benefit from ICIs.

Conclusions Genomic alteration signatures might define subsets of lung cancer tumors with no PD-L1 expression to complement TMB and PD-L1 on the selection criteria for patients whom may benefit from checkpoint inhibitors. Ethics Approval The study was approved by Neogenomics Institution’s Ethics Board and external IRB, approval number 420160280.

Conclusions Genomic alteration signatures might define subsets of lung cancer tumors with no PD-L1 expression to complement TMB and PD-L1 on the selection criteria for patients whom may benefit from checkpoint inhibitors. Ethics Approval The study was approved by Neogenomics Institution’s Ethics Board and external IRB, approval number 420160280.