Developmental medico-life-sciences, Journal Year: 2024, Volume and Issue: 1(8), P. 1 - 3
Published: Dec. 18, 2024
INTRODUCTIONOver the past decade, immunotherapy has redefined landscape for cancer treatment, providing unprecedented survival benefits across a broad swath of tumors. The ability to harness and modulate immune system transformed outcomes patients, from checkpoint inhibitors (ICIs) advanced cellular therapies, such as chimeric antigen receptor (CAR) T cells CAR macrophages (CAR-MΦ). However, these advancements have come with new challenges, variability in efficacy, toxicities, lack efficacy against immunosuppressive tumor microenvironment (TME), especially solid tumors[1]. In this editorial, we explore major advances immunotherapy, potential combination therapies CAR-MΦ, need approaches overcome evolving challenges. Immune Checkpoint Inhibitors: cancers melanoma, NSCLC, RCC, ICIs become cornerstone immunotherapy. block inhibitory receptors PD-1, PD-L1, CTLA-4, thereby enable suppression unleash effective anti-tumor response. many provided durable responses some patients survived more than five years. We landmark trials that show significant improvements overall (OS) progression-free (PFS) vs. chemotherapy metastatic refractory cancers[2]. Nevertheless, despite all advances, not respond ICIs. Resistance is due heterogeneity, evasion mechanisms, TME. addition, immune-mediated adverse events (images), including gastrointestinal, dermatologic, endocrine continue be barriers. Biomarker discovery PD-L1 expression mutational burden will increasingly important field evolves identifying most likely benefit personalized therapy minimal risk cost[3]. Cellular Therapies: CAR-T Cells Emerging Role CAR-MacrophagesHowever, are transformative; now frontier Remarkable success cells, which involve engineering express tumor-specific receptors, been shown hematologic malignancies, particularly leukemia lymphoma. Despite barriers, however, tumors still limited[4]. New CAR-MΦ emerging novel solution meet Chimeric engineered into capable targeting while modifying hostile After binds through phagocytosis, they actively engulf secreting pro-inflammatory cytokines reprogram TME immunostimulatory. addition stimulating other like natural killer (NK) also amplify responses[5]. Promising safety demonstrated by early clinical trials, those HER2-expressing can persist within tumor, physical synergize immunotherapies. Safety issues, remain, notably possibility cytokine release syndrome (CRS) macrophage activation (MAS)[6]. Macrophages' intrinsic role inflammation regulation, may provide controlled response cells. These risks being mitigated tailored strategies, IL-10 expression, ensure safe application[7]. Combination future strategies its limitations improve efficacy. preclinical models, synergistic activity anti-PD-L1 anti-CTLA-4. blockade reinvigorates exhausted remodels TME, making it hospitable sustained attack[8]. Efforts biochemical barriers equally required. Since secrete or enzymes digest extracellular matrix enhances cell infiltration persistence tumors, hypothesized could diphtheria toxin, elicits an site. Moreover, immunotherapies alone, when combined conventional radiotherapy, increase presentation, infiltration, response[9]. CONCLUSION Immunotherapy fundamentally changed how treated given who were once untreatable hope. remain promising innovation unique advantages because phagocytosing presenting antigens, reprogramming TME.A rational approach ICIs, treatments would future. Additionally, concerns addressed rigorous long-term follow-up optimize treatment strategies. As stand on brink frontier, challenge scientific community clear: needs refined expand reach, becomes mainstay care, offer cures where none existed before.
Language: Английский