ABSTRACT Immunotherapy (IMT) has emerged as a promising treatment strategy across a broad spectrum of human cancers, with multiple agents, particularly immune check point inhibitors, showing promising results in various types of cancers. Its full potential has yet to be realized, due in part, to a lack of biomarkers predicting response to treatment. Multiple immune and genomic biomarkers of response based on analysis of pre-treatment specimens have been described but most are not very robust with significant overlap between responders and non-responders. Therefore, there is a critical unmet need to perform comprehensive characterization of candidate biomarkers in early phase IMT trials using standardized assays and novel methodologies. Recognizing the need for comprehensive immune monitoring for IMT clinical trials, in 2017 NCI developed the Cancer Immune Monitoring and Analysis Center (CIMAC) and Cancer Immunologic Data Commons (CIDC) Network, with the goal of identifying biomarkers of response, resistance, and adverse events to optimize immunotherapy approaches for patients with cancer. The MD Anderson Cancer Immune Monitoring and Analysis Center (MDA-CIMAC) is one of four CIMAC sites established five years ago that has been standardizing genomic, pathology and immunology assays and supporting profiling of tissue and blood specimens from patients treated in IMT trials. The MDA-CIMAC will be co-led by Drs. Ignacio Wistuba, renowned cancer surgical and molecular pathologist, Gheath Al-Atrash, well-known medical oncologist with expertise in stem cell transplantation and immunotherapy, and Cara Haymaker, cancer immunologist with expertise in immune biomarker analysis. They will be supported by a multidisciplinary team of world-class and highly collaborative experts on cancer and immunotherapy. The main goals of MDA-CIMAC are to: 1) provide a centralized and harmonized platform for sample collection, processing and quality assurance, and 2) use analytically-validated and standardized (Tiers 1 and 2) and highly innovative (Tier 3) assays to offer analyses for phenotypic, genomic, and functional characterization of responses of patients enrolled on IMT clinical trials. In Aim 1, we will utilize Standard Operating Procedures (SOPs) following the developed CIMAC umbrella protocol to provide services for processing and distribution of annotated biospecimens from the NCI-sponsored early phase immunotherapy clinical trials and to link the specimens to relevant clinical, pathological, immune and molecular data within the CIMAC-CIDC Network. In Aim 2, we will perform routine and innovative pathological, immunological and molecular analyses using standardized and validated and highly innovative assays to aid the completion of NCI- sponsored early phase clinical trials and the development of novel predictive IMT biomarkers. In Aim 3, in conjunction with the CIDC team, we will provide biostatistics and computational services for data collection and analysis, an...