Targeting tumor-infiltrating tregs for improved antitumor responses.

Immunotherapies have revolutionized the landscape of cancer treatment. Regulatory T cells (Tregs), as crucial components of the tumor immune environment, has great therapeutic potential. However, nonspecific inhibition of Tregs in therapies may not lead to enhanced antitumor responses, but could also trigger autoimmune reactions in patients, resulting in intolerable treatment side effects. Hence, the precision targeting and inhibition of tumor-infiltrating Tregs is of paramount importance. In this overview, we summarize the characteristics and subpopulations of Tregs within tumor microenvironment and their inhibitory mechanisms in antitumor responses. Furthermore, we discuss the current major strategies targeting regulatory T cells, weighing their advantages and limitations, and summarize representative clinical trials targeting Tregs in cancer treatment. We believe that developing therapies that specifically target and suppress tumor-infiltrating Tregs holds great promise for advancing immune-based therapies.

Exploring CAR-T Cell Therapy Side Effects: Mechanisms and Management Strategies.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of malignancies, especially hematological tumors, but toxicities have tempered its success. The main impediments to the development of CAR-T cell therapies are the following: cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and on-target/off-tumor toxicity (OTOT). This review summarizes these side effects' underlying mechanisms and manifestations over time. It provides potential prevention and treatment according to the consensus grading, stressing the significance of establishing strategies that anticipate, reduce, and navigate the beginning of these side effects. It is essential to fully comprehend the mechanisms underlying these toxicities to create efficient treatment and preventive approaches.

gC1qR: A New Target for Cancer Immunotherapy.

Although breakthroughs in cancer treatment have been achieved, immunotherapy yields only modest benefits in most patients. There is still a gap in clarifying the immune evasiveness and immune-resistance mechanisms. Identifying other candidate targets for cancer immunotherapy is therefore a clear unmet clinical need. The complement system, a pillar of innate immunity, has recently entered the limelight due to its immunoregulatory functions in the tumor microenvironment (TME). In particular, gC1qR, a receptor for globular heads of C1q, serves as a promising new target and has attracted more attention. gC1qR, also named P32/C1qBP/HABP1, is a multifunctional protein that is overexpressed in various cancers and holds prognostic value. It regulates the tumorigenic, progression and metastatic properties of tumor cells through several downstream signaling pathways, including the Wnt/ß-catenin, PKC-NF-κB and Akt/PKB pathways. A few preclinical experiments conducted through gC1qR interventions, such as monoclonal antibody, chimeric antigen receptor T-cell (CAR-T) therapy, and tumor vaccination, have shown encouraging results in anticancer activity. The efficacy may rely on the regulatory role on the TME, induction of tumor cells apoptosis and antiangiogenic activity. Nevertheless, the current understanding of the relationship between cancer immunotherapy and gC1qR remains elusive and often contradictory, posing both opportunities and challenges for therapeutic translation in the clinic. In this review, we focus on the current understanding of gC1qR function in cancer immunology and highlight the vital roles in regulating the TME. We also examines the rationale behind targeting gC1qR and discusses the potential for translating into clinical practice.