Macrophage-Targeted Therapies
Drugs that work through the macrophage: CSF1R inhibitors, corticosteroids, anti-TNF biologics, and emerging targets.
Pexidartinib + chemotherapy: decreased tumor growth kinetics and pulmonary metastases by CD8+ T cell-dependent mechanism; CD8 cells do the work, but the macrophage was in the way.
CSF1R inhibition overcomes macrophage-mediated immunosuppression caused by CDK4/6 inhibitors; combination improves antitumor immunity.
Corticosteroids suppress macrophage activation in sarcoidosis. Methotrexate spares steroids. Anti-TNF biologics (infliximab, adalimumab) for refractory disease; dissolve granulomas by removing the TNF survival signal.
2026 review of CSF1R small molecule inhibitor landscape across oncology, inflammatory disease, liver injury, and neurodegeneration; structure-guided optimization strategies covered.
CSF1R pharmacological depletion used to improve precision of microglia genetic manipulation; tool paper with implications for CNS macrophage research. Cell Reports 2026.
Structure-guided discovery of selective CSF1R inhibitors targeting macrophage-driven hepatic inflammation in acute liver injury; potential therapeutic application.
2026 review of emerging sarcoidosis therapeutics targeting JAK/STAT, PI3K-AKT-mTORC1, and Th1/Th17.1 convergence; maps molecular rationale for each drug class under investigation.
Frontiers in Medicine 2026 review: corticosteroids remain first-line; steroid-sparing agents (methotrexate, azathioprine) and biologics (anti-TNF) reviewed against a backdrop of sarcoidosis heterogeneity; individualized treatment based on organ involvement and symptom severity. July 2026.
Int Immunopharmacol 2026 review mapping M1/M2 signaling pathways in COPD, asthma, pulmonary fibrosis, ARDS, and lung cancer; proposes precision intervention strategies targeting polarization switches as a disease-modifying approach across obstructive and fibrotic lung conditions.
Arch Bronconeumol 2026 review: current therapeutic landscape including JAK inhibitors, PDE-4 inhibitors, SGLT-2 inhibitors in cardiac sarcoidosis, and CHIT1 inhibition (Phase II); PREDMETH trial supporting methotrexate as first-line steroid-sparing; 2025 WASOG Position Paper arguing against corticosteroid-centered model.
Microbiol Spectr 2026: host-directed therapy approach; pharmacological inhibition of host survival and anti-apoptotic pathways boosts macrophage intracellular killing of Mtb, Legionella, and Listeria; highlights vulnerability of host-adapted pathogens to manipulation of macrophage death-pathway timing.
Int Immunopharmacol 2026: maps coexisting macrophage subsets (inflammatory, regulatory, reparative, fibrosis-associated) in intestinal microenvironment; argues for subset-selective rather than broad macrophage suppression; reviews immunomodulatory and regenerative therapeutic approaches targeting plasticity.
Adv Drug Deliv Rev 2026: comprehensive review of intracellular delivery strategies targeting macrophages; covers lipid nanoparticles, polymeric carriers, exosomes, and whole-cell approaches; addresses endosomal escape, payload stability, and safety profile optimisation for clinical translation of macrophage-directed immunotherapies.
Biomaterials 2026: fluorinated ionizable lipid nanoparticles (A1F5C5) achieve superior mRNA delivery to macrophages in vivo; used to generate CAR-macrophages that home to solid tumors and synergise with anti-PD-L1 checkpoint blockade; addresses a key barrier in CAR-M clinical translation (ex vivo manufacture).
Eur J Haematol 2026: cladribine (2-CDA) shows efficacy and acceptable tolerance in non-LCH histiocytoses (ECD, RDD); response rates and toxicity profile reviewed in a real-world cohort; positions cladribine as a therapeutic option in histiocyte-driven disease alongside vemurafenib for BRAF-mutant cases.
Burns Trauma 2026: diabetic wound chronicity driven by persistent M1 macrophage state and failure of M1-to-M2 transition; hyperglycaemia shifts macrophage metabolism toward aerobic glycolysis, NLRP3 inflammasome activation, and impaired efferocytosis; reviews precision interventions targeting glycometabolic reprogramming, lactate-LDH-MCT axis, and PKM2 stabilisation.
Int Immunopharmacol 2026: engineered nanoparticles including antioxidant nanozymes and extracellular vesicle systems reprogram macrophages toward tissue-repair phenotypes in diabetic foot ulcers; reviews multifunctional nanotherapeutic platforms modulating macrophage polarization to break chronic wound chronicity.
J Mater Chem B 2026: Mn-doped ceria nanoparticles scavenge intracellular ROS in macrophages and promote M2-like polarization with elevated IL-10; polarized macrophages then drive osteogenesis and angiogenesis via BMP-2 and VEGF paracrine signals; redox regulation of macrophage state as an engineering handle for bone repair.
Adv Healthc Mater 2026: apoptotic body-mimetic nanoparticles carrying antioxidants target macrophages and drive anti-inflammatory reprogramming via MAPK and metabolic pathway modulation in diabetic wounds; mimicking the phosphatidylserine signal of apoptotic cells as an engineering strategy to trigger macrophage efferocytic programs for wound resolution.
J Control Release 2026: targeted nanoparticle inhibits STING signaling in bone marrow macrophages, shifting M1 toward M2 phenotype and suppressing radiation-induced inflammation; STING inhibition as an engineering strategy to reprogram bone marrow macrophages and protect hematopoietic recovery after irradiation.
J Control Release 2026: itaconate-releasing polyester microparticles reduce IL-6 and IL-1beta secretion from macrophages and dendritic cells; metabolite delivery as a strategy for targeting myeloid cell-driven inflammation in autoimmune contexts; exploits the endogenous macrophage immunometabolite itaconate as a pharmacological payload.
Int Immunopharmacol 2026: ginsenoside Rb1 suppresses NF-kB activation in alveolar macrophages, reducing macrophage-derived extracellular vesicle-mediated epithelial barrier disruption in sepsis ALI; macrophage EV secretion as the effector arm linking macrophage activation to epithelial injury in acute lung injury.
Adv Healthc Mater 2026: phospholipid phase-separation gel physically separates wound surfaces and suppresses macrophage NF-kB-driven inflammation, preventing postoperative adhesions; macrophage immunomodulation as a design requirement in surgical biomaterials for adhesion prevention.
ACS Biomater Sci Eng 2026: silicon nitride nanofilm coatings polarize macrophages from M1 to M2 phenotype at implant surfaces, enhancing osseointegration by reducing inflammatory signaling and promoting bone regeneration; macrophage polarization as a tunable engineering parameter in implant surface design.
ACS Appl Bio Mater 2026: mannose-targeted liposomes sequentially deliver an immunomodulator for M2-to-M1 TAM repolarization followed by chemotherapy in TNBC; mannose receptor targeting of macrophages as a delivery strategy for priming the tumor immune microenvironment before cytotoxic therapy.
Angew Chem Int Ed 2026: TADF photosensitizer generates ROS triggering pyroptosis and cGAS-STING activation, driving M2-to-M1 macrophage repolarization alongside dendritic cell maturation and T cell infiltration; combines macrophage repolarization with innate immune pathway activation as a multi-arm photodynamic immunotherapy strategy.
J Control Release 2026: an asymmetric bilayer hydrogel dressing carries macrophage-targeting liposomes loaded with artemisinin conjugates and Cu2+; activates macrophage autophagy via PI3K/AKT/mTOR and AMPK/mTOR, restoring impaired autophagic flux in the hyperglycemic wound bed and accelerating diabetic foot ulcer repair.
J Control Release 2026: in mice, a nanodrug combining COX-2 proteolysis-targeting chimera with immunomodulatory payload degrades COX-2 via the ubiquitin-proteasome pathway and shifts synovial macrophages toward anti-inflammatory phenotypes, restoring cartilage thickness and reducing OA progression; dual targeting of enzyme and macrophage polarization as a strategy for chronic joint disease.