Programmed death 1 (PD-1) and its ligand (PD-L1) as a new frontier in cancer Immunotherapy and challenges for the Pathologist: state of the art.

The interest in better understanding the immune-microenvironment and tumor cells crosstalk, recently leads to focus on immune checkpoints role, notably on PD-1/PD-L1 axis. The current backdrop concerning cancer immunotherapy is constantly evolving and new biomarkers still need to be granted in this dynamic context. This review tries to get lights on PD-L1 complex scenario mainly focusing on troubling issues in assessing this marker in daily practice. It's still necessary to look deeper into this matter in order to make easier the pathologists-oncologist interaction.

Callea M ，Pedica F ，Doglioni C 《-》

Biomarkers for PD-1/PD-L1 Blockade Therapy in Non-Small-cell Lung Cancer: Is PD-L1 Expression a Good Marker for Patient Selection?

Immunotherapy has emerged as a promising treatment modality in cancer therapy. With improved understanding of how to tip the balance of immune homeostasis, novel therapeutics targeting immune checkpoints have been developed, with durable responses observed in multiple solid tumors, including melanoma, renal cell carcinoma, and non-small-cell lung cancer. Clinical trials have reported favorable responses using programmed cell death-1 protein receptor (PD-1)/programmed cell death-1 protein ligand (PD-L1) blockade as monotherapy and most impressively in combinatorial trials with cytotoxic T-lymphocyte antigen-4 protein blockade. Nonetheless, a clinical benefit has not been observed in all patients. Therefore, identifying the ideal biomarkers for patient selection would be of great value in optimizing and personalizing immunotherapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials and immunohistochemistry assays. In addition, the response to immune checkpoint inhibition has been complicated by PD-L1 expression as a marker influenced by the dynamic tumor microenvironment. No consensus has yet been reached on whether PD-L1 expression is an ideal marker for patient selection. Recent research has shown promise for alternative markers, including T-cell immunohistochemistry, other immunologic markers, T-cell receptor clonality, and somatic mutational burden. However, additional studies are needed to assess the value of these as practical predictive biomarkers for patient selection and treatment response.

Chae YK ，Pan A ，Davis AA ，Raparia K ，Mohindra NA ，Matsangou M ，Giles FJ ... -  《-》

PD-1/PD-L1 immune checkpoint: Potential target for cancer therapy.

Recent studies show that cancer cells are sometimes able to evade the host immunity in the tumor microenvironment. Cancer cells can express high levels of immune inhibitory signaling proteins. One of the most critical checkpoint pathways in this system is a tumor-induced immune suppression (immune checkpoint) mediated by the programmed cell death protein 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1). PD-1 is highly expressed by activated T cells, B cells, dendritic cells, and natural killer cells, whereas PD-L1 is expressed on several types of tumor cells. Many studies have shown that blocking the interaction between PD-1 and PD-L1 enhances the T-cell response and mediates antitumor activity. In this review, we highlight a brief overview of the molecular and biochemical events that are regulated by the PD-1 and PD-L1 interaction in various cancers.

Dermani FK ，Samadi P ，Rahmani G ，Kohlan AK ，Najafi R ... -  《-》

Predictive Biomarkers for Immunotherapy Response Beyond PD-1/PD-L1.

Darabi S ，Braxton DR ，Eisenberg BL ，Demeure MJ ... -  《ONCOLOGY-NEW YORK》

PD-1/PD-L1 and immunotherapy for pancreatic cancer.

Therapy that targets programmed death 1 or programmed death 1 ligand 1 (PD-1/PD-L1), which are known as immune checkpoints, has been recently rapidly developing as oncotherapy for various carcinomas. However, this therapy has a poor effect on the treatment of pancreatic cancer with PD-1/PD-L1 blockade monotherapy. In this review, the development and limitations of anti-PD-1/PD-L1 monotherapy in pancreatic cancer are discussed. We then consider the underlying mechanism of anti-PD-1/PD-L1 monotherapy failure, combination strategies overcoming resistance to anti-PD-1/PD-L1 immunotherapy and the prospect of targeting PD-1/PD-L1 for the immunotherapy of pancreatic cancer.

Feng M ，Xiong G ，Cao Z ，Yang G ，Zheng S ，Song X ，You L ，Zheng L ，Zhang T ，Zhao Y ... -  《-》