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ABC transporters affects tumor immune microenvironment to regulate cancer immunotherapy and multidrug resistance

Jingyi Fan1, Kenneth Kin Wah To2, Zhe-Sheng Chen3

  • 1State Key Laboratory of Oncology in South China；Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute; Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Department of pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing 100038, China.

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|December 4, 2022
PubMed

Insights

Multidrug resistance (MDR) in cancer involves cells resisting multiple drugs, often due to ATP-binding cassette (ABC) transporters. These transporters also impact the tumor immune microenvironment (TIME), affecting cancer treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Multidrug resistance (MDR) is a major challenge in cancer chemotherapy, leading to treatment failure.
  • ATP-binding cassette (ABC) transporters are key players in MDR by effluxing chemotherapeutic drugs from cancer cells.
  • ABC transporters are increasingly recognized for their role in modulating the tumor immune microenvironment (TIME).

Purpose of the Study:

  • To review recent advancements in understanding the dual role of ABC transporters in MDR and cancer immunity.
  • To highlight the interplay between ABC transporters, cytokines, and anti-tumor immunity.
  • To discuss the therapeutic potential of targeting ABC transporters to enhance cancer treatment.

Main Methods:

  • Literature review of current research on ABC transporters in cancer.
  • Analysis of studies investigating ABC transporter function in MDR.
  • Examination of research on ABC transporter regulation of the tumor immune microenvironment.

Main Results:

  • Overexpression of ABC transporters contributes significantly to MDR by reducing intracellular drug concentrations.
  • ABC transporters influence anti-tumor immunity by transporting cytokines and affecting immune cell function within the TIME.
  • Cytokines and immune signaling molecules regulate the expression of ABC transporters.

Conclusions:

  • Targeting ABC transporters offers a promising strategy to overcome MDR and improve chemotherapy outcomes.
  • Modulating ABC transporter activity can enhance the efficacy of immunotherapies, such as immune checkpoint inhibitors.
  • The intricate relationship between ABC transporters and the TIME presents new avenues for cancer therapy development.
Keywords:
ABC transporterMultidrug resistanceP-glycoproteinTargeted therapyTumor immune microenvironment

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