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Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
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Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma

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Rab37-mediated OPN secretion enriches SPP1+ macrophages through autocrine-paracrine signaling to drive lung tumor

You-En Yang1, Yu-An Lin2, Lun-Ling Ling1

  • 1Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Oncogenesis
|January 14, 2026
PubMed

Insights

Rab37 regulates lung tumor-associated macrophages (TAMs), promoting an immunosuppressive tumor microenvironment (TME) through osteopontin (OPN) secretion. Targeting Rab37-OPN may offer a new lung cancer therapy.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Tumor-associated macrophages (TAMs) are crucial regulators of the tumor microenvironment (TME) and cancer progression.
  • The molecular mechanisms driving TAM functional heterogeneity are not fully understood.
  • Rab37's role in macrophage programming within the lung TME requires elucidation.

Purpose of the Study:

  • To identify molecular determinants of TAM functional heterogeneity.
  • To investigate the role of Rab37 in regulating macrophage states within the lung TME.
  • To explore the therapeutic potential of targeting the Rab37-osteopontin axis in lung cancer.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) to analyze macrophage populations in Rab37 wild-type (WT) and knockout (KO) tumors.
  • Assessment of osteopontin (OPN) secretion and STAT3 signaling activation.
  • Analysis of lung cancer cell proliferation, migration, and invasion.
  • Clinical correlation analysis in patient-derived lung cancer specimens.

Main Results:

  • Rab37 deficiency shifted TAM populations from immunosuppressive Spp1+ to Thbs1+ phenotypes.
  • Rab37 promoted OPN secretion, activating STAT3 signaling and inducing M2-like macrophage polarization.
  • Paracrine OPN signaling enhanced lung cancer cell proliferation, migration, and invasion.
  • Co-expression of CD163, Rab37, and OPN in TAMs correlated with poor prognosis and recurrence in lung cancer patients.

Conclusions:

  • Rab37 is a key regulator of TAM phenotype and function, orchestrating OPN/STAT3 signaling.
  • Rab37 promotes an immunosuppressive TME and lung cancer progression.
  • The Rab37-OPN axis represents a potential therapeutic target for lung cancer treatment.

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