**1. Introduction**

The immune checkpoint cell surface proteins like programmed death-ligand 1 (PD-L1), programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CLTA-4) represent important pathways of cancer immune evasion. Immune checkpoint inhibitors (ICIs) are identified as potent key players in providing therapeutic benefit in a range of solid cancers as well as in a subgroup of hematological malignancies. However, the response rates to these immune-modulatory molecules are sub-optimal and predictive biomarkers allowing to select for responsive cancer patients are lacking. The study of the dynamics of the immune system and of the tumors under immune checkpoint blockade has greatly improved knowledge on the mechanisms of action of ICIs, allowing the identification of a number of novel candidate dynamic biomarkers predictive of ICI treatment response meriting further exploration in validation trials.

Tumor biopsy of tissue from primary or metastatic site is a major mainstay of treatment decisions as the molecular features and histology can reveal the complex cancer landscape. However, tissue biopsy has various limitations such as high heterogeneity, invasive nature of tissue sampling and skilled expertise/techniques required for analyzing and reporting making it a difficult specimen especially for treatment monitoring purpose [1]. Therefore, emphasis on utility of liquid biopsies as prognostic and predictive soluble biomarkers especially in cancer immunotherapy is gaining a lot of attention. The main advantages of blood-based specimens are that these are easy to extract and analyze with limited skilled expertise or techniques. Furthermore, biomarkers in the blood can represent dynamic alterations of the evolving cancer in response to treatment and can help in longitudinal monitoring. In addition to this, these can also be utilized for risk prediction of immune-related adverse events (irAE) which is an important and critical monitoring parameter [2].

In this chapter, we attempt to discuss in relevant details the purpose and role of immune modulatory molecules and of the different serum soluble biomarkers in various human and animal models with an aim to show insight on to their mechanisms of action and resistance, thus conveying information predictive of therapeutic response.
