ArticleCancer research2026
Regression-Associated Macrophages Recruit Natural Killer Cells That Constrain Targeted Therapy Resistance.
Article in Cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Targeted kinase inhibitors induce marked tumor regressions but are limited by the emergence of drug-tolerant residual disease and resistance. Although tumor-intrinsic and adaptive immune mechanisms have been extensively studied, a better understanding of the contribution of innate immunity to targeted therapy durability is needed to devise optimal treatment strategies. In this study, we showed that natural killer (NK) cells constrain targeted therapy resistance and identified a regression-associated macrophage program that promotes NK cell recruitment. In immunocompetent melanoma models that recapitulate patient treatment trajectories, tumor regression was characterized by robust NK infiltration, which transitioned to an NK-excluded residual state preceding resistance. A regression-associated macrophage subset (F4/80high CCL5+ MHC class II+ CD63+) contributed to NK cell recruitment via CCR2/5 signaling. Genetic depletion of macrophages using LysM-cre;iDTR mice impaired NK cell infiltration. Pharmacologic inhibition of protein tyrosine phosphatase nonreceptor type 22 (Ptpn22), a negative regulator of immune activation, reprogrammed the residual tumor microenvironment, restored NK cell recruitment, and delayed resistance onset. An analysis of data from patients with melanoma and lung cancer revealed concordant NK dynamics during therapy, linking this innate immune program to clinical outcomes. These findings identify innate immune remodeling as a key contributor to targeted therapy durability and identify NK cell recruitment, promoted in part by regression-associated macrophages, as a therapeutically actionable node for extending the durability of response across oncogene-driven cancers. SIGNIFICANCE: Natural killer cells recruited by regression-associated macrophages delay resistance to targeted therapies, highlighting the role of innate immune remodeling in targeted therapy durability and providing a strategy to prolong treatment efficacy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.