Cromolyn

A review.The goals of treatment in MCD include avoidance of known triggers; treatment of the underlying pathol. when known; and pharmacotherapy targeting mast cell mediators such as with H1 and H2 histamine receptor blockers, leukotriene pathway modifiers, and mast cell stabilizers (which traditionally include cromolyn and ketotifen but may also be expanded to include calcineurin inhibitors and currently investigational agents such as Bruton tyrosine kinase [BTK] inhibitors).Well-designed prospective trials are needed to gain more information on the effect of omalizumab on mastocytosis and idiopathic anaphylaxis and determine the best approach to preventive therapy of anaphylaxis in these patient populations.Those subsets of patients with severe anaphylaxis or MCAS (with or without known mastocytosis) and an IgE-dependent trigger identified at diagnosis or during follow-up who experience breakthrough severe MCA events despite their best efforts at trigger avoidance and preventive antimediator therapy appear particularly well suited to benefit from omalizumab therapy.

Pancreatic ductal adenocarcinoma (PDAC) exhibits an immunosuppressive tumor microenvironment (TME) contributing to its therapeutic resistance. Following our previous studies, we report that mast cells infiltrating the PDAC TME foster this immunosuppression and desmoplasia. Mast cell infiltration correlated with human PDAC progression, and genetic or pharmacological mast cell depletion reduced tumor growth and desmoplasia while enhancing survival in mouse PDAC models. Mechanistically, mast cell-derived IL-10 promoted PDAC progression. Strikingly, combining an agonistic anti-OX40 immunotherapy with mast cell blockade synergistically elicited durable anti-tumor immunity, marked by increased infiltration of CD8⁺ T effector cells expressing granzyme B and dramatic survival benefit unachievable with either approach alone. An OX40-associated gene signature correlated with improved survival in human PDAC, supporting therapeutic translation. Our findings establish mast cells as promoters of the suppressive PDAC TME and rational targets for combination immunotherapy. Targeting this mast cell-mediated resistance mechanism could overcome immunotherapy failure in PDAC.