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Updated: Jun 2, 2026

Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
07:36

Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody

Published on: May 16, 2020

Antibody targeting of the TNF-TNFR2 axis to overcome tumor immune resistance

Xiaozhen Kang1, Xiangmin Tong1,2, Shibing Wang1,2

  • 1Zhejiang Key Laboratory of Zero Magnetic Medicine, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.

Frontiers in Immunology
|June 1, 2026
PubMed

Insights

Tumor Necrosis Factor Receptor 2 (TNFR2) drives cancer growth and immune evasion. Targeting TNFR2 offers a novel strategy to overcome resistance to cancer immunotherapies by remodeling the tumor microenvironment.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Tumor Necrosis Factor (TNF) has dual roles in cancer, mediated by TNFR1 and TNFR2.
  • TNFR2 promotes tumor inflammation and immune suppression within the tumor microenvironment (TME).
  • TNFR2 is expressed on various cells in the TME, including Tregs, MDSCs, CAFs, and cancer cells, contributing to immune evasion and resistance to immune checkpoint blockade (ICB).

Purpose of the Study:

  • To review the distinct signaling pathways of TNFR1 and TNFR2.
  • To explore therapeutic strategies targeting the TNF-TNFR2 axis for cancer treatment.
  • To discuss challenges and future directions for clinical translation of TNFR2-targeted therapies.

Main Methods:

  • Review of existing literature on TNF, TNFR1, and TNFR2 signaling.
  • Analysis of structural and functional differences between transmembrane and soluble TNF.
  • Examination of emerging therapeutic approaches targeting the TNF-TNFR2 axis.

Main Results:

  • TNFR2 signaling predominantly supports tumor progression and immunosuppression.
  • Therapeutic strategies like antibodies and ADCs aim to selectively target the TNF-TNFR2 axis.
  • Targeting TNFR2 can remodel the immunosuppressive TME and potentially overcome ICB resistance.

Conclusions:

  • TNFR2 is a key mediator of tumor-promoting inflammation and immune evasion.
  • Targeting the TNF-TNFR2 axis presents a promising strategy to enhance cancer immunotherapy efficacy.
  • Overcoming challenges like on-target toxicity and patient stratification is crucial for clinical success.
Keywords:
TNFTNFR2antibodyimmune resistanceimmunotherapy

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