The main goal of the current project is to design and develop a multipronged functional proteomics strategy, with translation into the clinic, for deciphering all the microenvironment protein factors involved in the dysfunction of the immune system in MBLhi and CLL patients in order to understand the disease better and design effective treatment and management strategies. This novel strategy will be performed by a systematic and comprehensive integration of complementary functional proteomics approaches which include antigen presentation and recognition by Immunopeptidomics. In this work, different protein extraction methods (Protocol A and Protocol B) and different immunoprecipitation (IP) solid supports (Protocol #1 and Protocol #2) are performed, using four tumor cell lines as a model. The study samples will be identified by the name of the cell line, followed by the number of the IP protocol used, followed by the letter corresponding to the protein extraction protocol used. H460_1A: 0520_1_2 H460_1B: 0520_2_1 JURKAT_1A: 0520_3_1 JURKAT_1B: 0520_4_1 H460_2B: 0520_5_1 CACO-2_2B: 0520_6_1 MDA-MB-231_2B: 0520_7_1