Therapeutic Strategies and Targets to Improve the Efficacy of PD-1/PD-L1 Blockade

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 25 July 2024 | Viewed by 11829

Special Issue Editor


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Guest Editor
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, China
Interests: cancer immunotherapy; immune checkpoint; tumor microenvironment; vaccine; peptide

Special Issue Information

Dear Colleagues,

Programmed cell death protein 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) are the hottest drug targets in cancer immunotherapy. Increasing numbers of researches are focusing on the combination therapies to cope with the low average response rate of PD-1/PD-L1 antibody blockade therapy in cancer and other indications. The combinational strategies include the use of Toll-like receptor (TLRs) and STING agonist vaccines, cytokines, nanomedicines, radiotherapy or chemotherapy to activate the innate immunity or induce tumor cell death. In addition, the combination with various targets and their drugs to achieve the purpose of activating innate and adaptive immunity are ongoing. These targets may play a role from different perspectives, such as the phagocytic targets CD47/SIRPa and CD24/Siglec-10 that modulate the function of macrophages, the NKG2 and KIR members that affect the function of NK cells, the targets hinder the function of immunosuppressive MDSC or Treg cells, CD73 and CD39 affects the adenosine metabolism, CD36 and CD38 that regulate the lipid metabolism, and the angiogenesis signaling VEGF/VEGFRs that affects the vascular angiogenesis and normalization to impact the infiltration of immune cells in tumor microenvironment. Drugs of these targets may focus on not only antibodies, but the fusion proteins, peptide drugs, small molecule drugs, aptamers, PROTAC and nanomedicines.

This Special Issue aims to improve the efficacy of PD-1/PD-L1 blockade in cancer and expand the knowledge on a wide range of topics in this field. The journal Pharmaceuticals now invites you to contribute review or original research articles covering the different facets of the combination therapy, which will be published as a Special Issue on “Therapeutic Strategies and Targets to Improve the Efficacy of PD-1/PD-L1 Blockade”.

Prof. Dr. Yanfeng Gao
Guest Editor

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Keywords

  • PD-1/PD-L1
  • immune checkpoint
  • radiotherapy
  • chemotherapy
  • targeted therapy
  • angiogenesis
  • vaccine
  • TLR
  • STING
  • metabolism

Published Papers (3 papers)

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Research

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15 pages, 4739 KiB  
Article
Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response
by Chen Ling, Xiuman Zhou, Yanfeng Gao and Xinghua Sui
Pharmaceuticals 2022, 15(5), 605; https://doi.org/10.3390/ph15050605 - 14 May 2022
Cited by 1 | Viewed by 2309
Abstract
A low response rate limits the application of immune checkpoint inhibitors (ICIs) in the treatment of esophageal adenocarcinoma (EAC), which requires the precise characterization of heterogeneous tumor microenvironments. This study aimed to identify the molecular features and tumor microenvironment compositions of EAC to [...] Read more.
A low response rate limits the application of immune checkpoint inhibitors (ICIs) in the treatment of esophageal adenocarcinoma (EAC), which requires the precise characterization of heterogeneous tumor microenvironments. This study aimed to identify the molecular features and tumor microenvironment compositions of EAC to facilitate patient stratification and provide novel strategies to improve clinical outcomes. Here, we performed consensus molecular subtyping with nonnegative matrix factorization (NMF) using EAC data from the Cancer Genome Atlas (TCGA) and identified two distinct subtypes with significant prognostic differences and differences in tumor microenvironments. The findings were further validated in independent EAC cohorts and potential response to ICI therapy was estimated using Tumor Immune Dysfunction and Exclusion (TIDE) and SubMap methods. Our findings suggest that EAC patients of subtype 2 with low levels of cancer-associated fibroblasts, tumor associated macrophages (TAMs), and MDSCs in the tumor microenvironment may benefit from PD-1 blockade therapy, while patients of subtype 1 are more responsive to chemotherapy or combination therapy. These findings might improve our understanding of immunotherapy efficacy and be useful in the development of new strategies to better guide immunotherapy and targeted therapy in the treatment of EAC. Full article
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Review

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16 pages, 3198 KiB  
Review
Revolutionization in Cancer Therapeutics via Targeting Major Immune Checkpoints PD-1, PD-L1 and CTLA-4
by Pratibha Pandey, Fahad Khan, Huda A. Qari, Tarun Kumar Upadhyay, Abdulhameed F. Alkhateeb and Mohammad Oves
Pharmaceuticals 2022, 15(3), 335; https://doi.org/10.3390/ph15030335 - 9 Mar 2022
Cited by 39 | Viewed by 6218
Abstract
Numerous research reports have witnessed dramatic advancements in cancer therapeutic approaches through immunotherapy. Blocking immunological checkpoint pathways (mechanisms employed by malignant cells to disguise themselves as normal human body components) has emerged as a viable strategy for developing anticancer immunity. Through the development [...] Read more.
Numerous research reports have witnessed dramatic advancements in cancer therapeutic approaches through immunotherapy. Blocking immunological checkpoint pathways (mechanisms employed by malignant cells to disguise themselves as normal human body components) has emerged as a viable strategy for developing anticancer immunity. Through the development of effective immune checkpoint inhibitors (ICIs) in multiple carcinomas, advances in cancer immunity have expedited a major breakthrough in cancer therapy. Blocking a variety of ICIs, such as PD-1 (programmed cell death-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) has improved the immune system’s efficacy in combating cancer cells. Recent studies also supported the fact that ICIs combined with other potent antitumor candidates, such as angiogenic agents, could be a solid promising chemopreventive therapeutic approach in improving the effectiveness of immune checkpoint inhibitors. Immune checkpoint blockade has aided antiangiogenesis by lowering vascular endothelial growth factor expression and alleviating hypoxia. Our review summarized recent advances and clinical improvements in immune checkpoint blocking tactics, including combinatorial treatment of immunogenic cell death (ICD) inducers with ICIs, which may aid future researchers in creating more effective cancer-fighting strategies. Full article
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Other

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8 pages, 1849 KiB  
Case Report
Good Response of Advanced Thymic Carcinoma with Low PD-L1 Expression to Chemotherapy plus Pembrolizumab as First-Line Therapy and to Pembrolizumab as Maintenance Therapy: A Case Report
by Yoichi Nishii, Kazuki Furuhashi, Kentaro Ito, Tadashi Sakaguchi, Yuta Suzuki, Kentaro Fujiwara, Taro Yasuma, Tetsu Kobayashi, Corina N. D’Alessandro-Gabazza, Esteban C. Gabazza, Osamu Taguchi and Osamu Hataji
Pharmaceuticals 2022, 15(7), 889; https://doi.org/10.3390/ph15070889 - 19 Jul 2022
Cited by 4 | Viewed by 2330
Abstract
Thymic carcinoma is a rare malignant tumor with a poor prognosis. No standard treatment is currently available. The present case was a 64-year-old male smoker with no symptoms referred to our hospital because of abnormal chest radiological findings. The CT study showed a [...] Read more.
Thymic carcinoma is a rare malignant tumor with a poor prognosis. No standard treatment is currently available. The present case was a 64-year-old male smoker with no symptoms referred to our hospital because of abnormal chest radiological findings. The CT study showed a tumor between the anterior mediastinum and the right lung upper lobe, multiple nodular shadows along the right pleura, and pleural effusion. A CT-guided needle biopsy revealed squamous cell carcinoma. However, the differential diagnosis between thymic carcinoma and primary lung cancer was difficult. Treatment with carboplatin, nanoparticle albumin-bound paclitaxel, and pembrolizumab was initiated. The CT scan showed tumor shrinkage and good clinical response after four treatment cycles. Therapy was switched to maintenance therapy with pembrolizumab alone. Imaging studies showed further tumor shrinkage after twelve cycles of maintenance therapy with pembrolizumab. Sixteen cycles of maintenance therapy were continued without performance status deterioration. An abnormal radiological finding was detected after a twelve-month exacerbation-free period. The diagnosis was thymic carcinoma. Treatment with lenvatinib was initiated, and tumor-size reduction was observed. This is the first report of a case showing a successful maintenance therapy with pembrolizumab after effective first-line therapy with a combination of carboplatin-based chemotherapy plus pembrolizumab in advanced thymic carcinoma. Full article
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