Gemcitabine and checkpoint blockade exhibit synergistic anti-tumor effects in a model of murine lung carcinoma.

Abstract

Lung cancer is leading cause of cancer death in the world. Chemotherapy is currently one of the standard treatments for lung cancer. Gemcitabine is a pyrimidine nucleoside drug which has been approved by FDA to treat lung cancer. However, acquired resistance inevitable develops after Gemcitabine treatment, limiting clinical efficacy. Lewis lung carcinoma (LLC) cells were treated with Gemcitabine and cell apoptosis and programmed cell death-ligand 1 (PD-L1) expression were analyzed by flow cytometry. LLC mouse model was established to analysis the proportion and programmed cell death-1 (PD-1) expression of CD8 + T cells. Anti-tumor effect by treating with Gemcitabine and anti-PD-1 antibody was measured through in vivo LLC mouse model. Gemcitabine treatment induces tumor cell apoptosis and PD-L1 expression. Further study showed that Gemcitabine treatment also increases CD8+ and CD4+ T cells proportion, PD-1 and PD-L1 expression in LLC mouse model. Combination therapy with Gemcitabine and αPD-1 not only has strong anti-tumor effect, but also could inhibit postsurgical recurrence of LLC. Our findings demonstrated that the combination therapy of Gemcitabine and αPD-1 is an effective therapeutic strategy for lung cancer.

• Authors: Bin Du, Xiaojiao Wen, Yao Wang, Mengxin Lin, Jinhuo Lai
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 86 Pg. 106694 (Sep 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 32570034 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• Antineoplastic Agents, Immunological
• B7-H1 Antigen
• Cd274 protein, mouse
• Immune Checkpoint Inhibitors
• Pdcd1 protein, mouse
• Programmed Cell Death 1 Receptor
• Deoxycytidine
• Gemcitabine

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology, therapeutic use)
• Antineoplastic Agents, Immunological (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• B7-H1 Antigen (biosynthesis)
• CD4-Positive T-Lymphocytes (metabolism)
• CD8-Positive T-Lymphocytes (metabolism)
• Carcinoma, Lewis Lung (drug therapy, immunology)
• Cell Line, Tumor
• Deoxycytidine (analogs & derivatives, pharmacology, therapeutic use)
• Disease Models, Animal
• Drug Synergism
• Immune Checkpoint Inhibitors (pharmacology, therapeutic use)
• Lymphocytes, Tumor-Infiltrating (metabolism)
• Mice, Inbred C57BL
• Neoplasm Recurrence, Local (drug therapy)
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, biosynthesis, genetics)
• Tumor Microenvironment (drug effects, immunology)
• Up-Regulation
• Gemcitabine