**Author details**

*Advances in Precision Medicine Oncology*

**Acronyms and abbreviations**

TCR T cell receptor

Tex exhausted T cells Teff effector T cells

CRP C-reactive protein LDH lactate dehydrogenase OS overall survival

ICI immune checkpoint inhibitors PD-L1 programmed death-ligand 1 PD-1 programmed death- 1

TME tumor microenvironment

LAG-3 lymphocyte-activation gene-3

ALC absolute lymphocyte count MDSCs myeloid derived suppressor cells TAM tumor-associated macrophages irAE immune-related adverse events

NLR neutrophil-to-lymphocyte ratio

NSCLC non-small-cell lung cancer PFS progression free survival

dNLR derived Neutrophil-to-lymphocyte ratio

CTLA-4 cytotoxic T-lymphocyte-associated protein 4

TIM-3 T-cell immunoglobulin and mucin-domain containing-3

TIGIT T cell immunoreceptor with Ig and ITIM domains

can be modulated by immune checkpoint blockade and more specifically PD-1 and CTLA-4 inhibitors. We have summarized all the findings obtained in pre-clinical and clinical trials reporting an impact of anti-PD-1 and anti-CTLA-4 on intra-tumoral and peripheral immune response. Interestingly, the study of the dynamics of the immune system under CTLA-4 and PD-1 inhibitors shows a noticeable distinction in their regulatory mode of action on the anti-tumoral and peripheral immune response. Moreover, the findings discussed in this chapter show that CTLA-4 and PD-1 inhibitors do not only restore intra-tumoral effector T cells activity upon exhaustion but are also able to induce a consequential remodeling of the tumor microenvironment as well as the systemic immune response. Indeed, the field of immunological liquid biomarkers is fast evolving with many novel predictive and prognostics markers gaining attention. Though, liquid biopsies have many advantages including minimal invasiveness, longitudinal monitoring and simultaneous parallel testing with highly sensitive/ specific high throughput applications. Although several studies state the utility of soluble ICIs markers, it is observed that the characteristic feature of these markers is to modulate the immune response in synergy with each other. This makes them attractive candidates as up and down regulation of a combination of markers can allow better understanding of the immune modulatory and dynamic nature of soluble immune molecules involved in ICIs treatment. However, there are several limitations that need to be addressed for these markers. Mainly, standardization of sampling/measurement techniques as well as larger validation studies are required to verify the utility of these markers as promising tools to guide and monitor treatment decisions in ICIs treated patients. Finally, identification of dynamic biomarkers for prediction of ICIs tumor control and for monitoring of patient response under treatment is gaining considerable knowledge through recent technologies including proteomics and transcriptomics. Progress along this approach is critical to build reasoning for novel therapeutic combinations and to set forth a more personalized cancer immunotherapeutic strategy.

**42**

Afsheen Raza1,2†, Maysaloun Merhi1,2†, Allan Relecom3†, Queenie Fernandes1,5†, Varghese Inchakalody1,2†, Abdul Rahman Zar Gul2 , Shahab Uddin4 , Mohammed Ussama Al Homsi2 and Said Dermime1,2\*

1 Translational Cancer Research Facility and Clinical Trial Unit, Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar

2 National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar

3 Department of Oncology, Geneva University Hospitals, Geneva, Switzerland

4 Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar

5 College of Medicine, Qatar University, Doha, Qatar

\*Address all correspondence to: sdermime@hamad.qa

† These authors equally contributed in writing this book chapter.

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
