Tremendous progress has been achieved in the field of immune checkpoint inhibitors (ICIs) therapy in lung cancer in recent years. To generate robust, long-lasting anti-tumor immune responses in lung cancer patients, combinational ICI therapies have been explored deeply. Conventionally, chemotherapy was considered as immunosuppressive. It is now recognized that chemotherapy could also reinstate cancer cell immune-surveillance and enable the perception of cancer cells as dangerous. That is to say that chemotherapeutic drugs are not only a source of direct cytotoxic effects but also an adjuvant for anti-tumor immunity. Recently, multiple clinical studies of ICIs combined with chemotherapeutic drugs have been explored and proved effective. However, there are still crucial questions that are not well addressed, such as the optimal dose and schedule for a given combination may differ across disease indications, and the appropriate strategy of selecting patient population that can benefit from ICIs remains unclear. To facilitate more rational lung cancer ICIs therapy development, this review summarizes the immune-regulatory effects and related mechanisms of chemotherapeutic drugs and the clinical progress of ICIs and their combination with chemotherapies in lung cancer treatment.

Latanoprost is a kind of PGF 2α analogues, which is now one of the first-choice drugs in the clinic for open angle glaucoma and ocular hypertension. However, the previous synthetic methods have problems of long steps, low yield and difficult separation of isomeric impurities. Herein, we report a novel method for the synthesis of latanoprost in ten steps. Benzoyl Corey lactone as starting material was oxidized to form corresponding aldehyde by Dess-Martin oxidation. The ω side chain was bonded by improving Horner-Wadsworth-Emmons reaction with dimethyl(2-oxo-4-phenylbutyl)phosphonate and lithium chloride, and reduced with (-)-diisopinocampheyl chloroborane at -30 ℃ because of its greater selectivity towards the production of desired S-isomer (95%). The deprotection step wherein the protecting group of benzoyl on the hydroxyl group of the cyclopentane ring was removed, was preferably carried out by potassium carbonate in methanol. The hydrogenation of double bond in ω side chain was carried out by using 5% palladium-carbon as catalyst. The tetrahydropyranyl (THP) group was used for the protection of the diol with p-toluenesulfonic acid as catalyst. Latanoprost lactol was obtained by reducing the lactone with diisobutylaluminum hydride (DIBAL) at -78 ℃. α side chain of latanoprost was bonded by Wittig reaction with 4-carboxybutyl triphenylphosphoium bromide and NaHMDS forming phosphorus ylide. The carboxylic acid was alkylated with isopropyl iodide in the presence of 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU), and then removed the THP protecting groups with pyridinium 4-toluenesulfonate (PPTS). Latanoprost was separated from two isomers of 15(S)-latanoprost and 5,6-trans-latanoprost after purification by normal-phase high performance liquid chromatography. Thus latanoprost was obtained with high purity of 99.91% and high overall yield of 19.2%, and the structure was characterized by 1 H NMR, 13 C NMR, IR and HRMS. Compared with the previous routes, the current synthesis is shorter, more practical, and more suitable for large-scale preparation.