Modulation of Tumor-Associated Macrophages to Overcome Immune Suppression in the Hepatocellular Carcinoma Microenvironment.

Simple Summary: Tumor-associated macrophages (TAMs) represent a challenge in developing an effective and safe therapy for HCC. TAMs are considered to be one of the major mechanisms for HCC resistance to current therapies. TAMs, known as M1-like and M2-like macrophages, were discovered to be subdivided into four subsets (M2a, M2b, M2c, and M2d). Each subset has a hypothetical contribution as a TAM immunosuppressive cell. Several trials have studied removing or modulating the immune suppressive roles of TAMs in the HCC microenvironment. Identifying TAMs' behavior and subsets may be crucial for modulating the immune suppression in the HCC microenvironment. Hepatocellular carcinoma (HCC) is a major global health issue characterized by poor prognosis and complex tumor biology. One of the critical components of the HCC tumor microenvironment (TME) is tumor-associated macrophages (TAMs), which play a pivotal role in modulating tumor growth, immune evasion, and metastasis. Macrophages are divided into two major subtypes: pro-inflammatory M1 and anti-inflammatory M2, both of which may exist in TME with altered function and proportion. The anti-inflammatory M2 macrophages are further subdivided into four distinct immune suppressive subsets. TAMs are generally counted as M2-like macrophages with altered immune suppressive functions that exert a significant influence on both cancer progression and the ability of tumors to escape immune surveillance. Their involvement in modulating immune responses via different mechanisms at the local and systemic levels has made them a key target for therapeutic interventions seeking to enhance treatment outcomes. How TAMs' depletion influences immune responses in cancer is the primary interest in cancer immunotherapies. The purpose of this review is to delve into the recent progress made in TAM-targeting therapies. We will explore the current theories, benefits, and challenges associated with TAMs' depletion or inhibition. The manuscript concludes with future directions and potential implications for clinical practice. [ABSTRACT FROM AUTHOR]