Molecular pathways: Oncologic pathways and their role in T-cell exclusion and immune evasion - A new role for the AXL receptor tyrosine kinase

Todd A. Aguilera, Amato J. Giaccia

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

With the clinical impact of CTLA-4 and PD-1/PD-L1 immune checkpoint therapies, widespread interest in cancer immunotherapy has been ignited. However, the rate and extent of clinical responses to approved therapies are limited and often nonexistent in many solid tumors. This is partially because immune checkpoint therapies are most effective against T-cell-inflamed tumors, and non-T-cell-inflamed or T-cell-excluded tumors remain a significant barrier. New strategies are needed to overcome immune resistance mechanisms that arise during tumor development, which result in T-cell exclusion. Approaches may need to be combined with conventional therapies such as chemotherapy, radiotherapy, and molecularly targeted therapy, and many clinical trials are ongoing. This review discusses the challenge of T-cell exclusion and innate oncologic pathways that contribute to this problem, including β-catenin, STAT3, NF-κB, PTEN, and AXL tyrosine kinase. The GAS6/AXL pathway is of interest immunologically, as its targeting can lead to greater antitumor immune responses after radiotherapy. In addition, several targeted therapies that are selective and nonselective for AXL are in preclinical and clinical development in acute myelogenous leukemia and renal cell cancer. There remains much to learn, but the future is bright for anti-AXL therapies, though effective combinations and their impact may not be realized for years to come.

Original languageEnglish (US)
Pages (from-to)2928-2933
Number of pages6
JournalClinical Cancer Research
Volume23
Issue number12
DOIs
StatePublished - Jun 15 2017

Fingerprint

Immune Evasion
Receptor Protein-Tyrosine Kinases
T-Lymphocytes
Neoplasms
Therapeutics
Radiotherapy
Catenins
Renal Cell Carcinoma
Acute Myeloid Leukemia
Protein-Tyrosine Kinases
Immunotherapy
Clinical Trials
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{9b6a66aa725744bea066f10b0c46520f,
title = "Molecular pathways: Oncologic pathways and their role in T-cell exclusion and immune evasion - A new role for the AXL receptor tyrosine kinase",
abstract = "With the clinical impact of CTLA-4 and PD-1/PD-L1 immune checkpoint therapies, widespread interest in cancer immunotherapy has been ignited. However, the rate and extent of clinical responses to approved therapies are limited and often nonexistent in many solid tumors. This is partially because immune checkpoint therapies are most effective against T-cell-inflamed tumors, and non-T-cell-inflamed or T-cell-excluded tumors remain a significant barrier. New strategies are needed to overcome immune resistance mechanisms that arise during tumor development, which result in T-cell exclusion. Approaches may need to be combined with conventional therapies such as chemotherapy, radiotherapy, and molecularly targeted therapy, and many clinical trials are ongoing. This review discusses the challenge of T-cell exclusion and innate oncologic pathways that contribute to this problem, including β-catenin, STAT3, NF-κB, PTEN, and AXL tyrosine kinase. The GAS6/AXL pathway is of interest immunologically, as its targeting can lead to greater antitumor immune responses after radiotherapy. In addition, several targeted therapies that are selective and nonselective for AXL are in preclinical and clinical development in acute myelogenous leukemia and renal cell cancer. There remains much to learn, but the future is bright for anti-AXL therapies, though effective combinations and their impact may not be realized for years to come.",
author = "Aguilera, {Todd A.} and Giaccia, {Amato J.}",
year = "2017",
month = "6",
day = "15",
doi = "10.1158/1078-0432.CCR-17-0189",
language = "English (US)",
volume = "23",
pages = "2928--2933",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

TY - JOUR

T1 - Molecular pathways

T2 - Oncologic pathways and their role in T-cell exclusion and immune evasion - A new role for the AXL receptor tyrosine kinase

AU - Aguilera, Todd A.

AU - Giaccia, Amato J.

PY - 2017/6/15

Y1 - 2017/6/15

N2 - With the clinical impact of CTLA-4 and PD-1/PD-L1 immune checkpoint therapies, widespread interest in cancer immunotherapy has been ignited. However, the rate and extent of clinical responses to approved therapies are limited and often nonexistent in many solid tumors. This is partially because immune checkpoint therapies are most effective against T-cell-inflamed tumors, and non-T-cell-inflamed or T-cell-excluded tumors remain a significant barrier. New strategies are needed to overcome immune resistance mechanisms that arise during tumor development, which result in T-cell exclusion. Approaches may need to be combined with conventional therapies such as chemotherapy, radiotherapy, and molecularly targeted therapy, and many clinical trials are ongoing. This review discusses the challenge of T-cell exclusion and innate oncologic pathways that contribute to this problem, including β-catenin, STAT3, NF-κB, PTEN, and AXL tyrosine kinase. The GAS6/AXL pathway is of interest immunologically, as its targeting can lead to greater antitumor immune responses after radiotherapy. In addition, several targeted therapies that are selective and nonselective for AXL are in preclinical and clinical development in acute myelogenous leukemia and renal cell cancer. There remains much to learn, but the future is bright for anti-AXL therapies, though effective combinations and their impact may not be realized for years to come.

AB - With the clinical impact of CTLA-4 and PD-1/PD-L1 immune checkpoint therapies, widespread interest in cancer immunotherapy has been ignited. However, the rate and extent of clinical responses to approved therapies are limited and often nonexistent in many solid tumors. This is partially because immune checkpoint therapies are most effective against T-cell-inflamed tumors, and non-T-cell-inflamed or T-cell-excluded tumors remain a significant barrier. New strategies are needed to overcome immune resistance mechanisms that arise during tumor development, which result in T-cell exclusion. Approaches may need to be combined with conventional therapies such as chemotherapy, radiotherapy, and molecularly targeted therapy, and many clinical trials are ongoing. This review discusses the challenge of T-cell exclusion and innate oncologic pathways that contribute to this problem, including β-catenin, STAT3, NF-κB, PTEN, and AXL tyrosine kinase. The GAS6/AXL pathway is of interest immunologically, as its targeting can lead to greater antitumor immune responses after radiotherapy. In addition, several targeted therapies that are selective and nonselective for AXL are in preclinical and clinical development in acute myelogenous leukemia and renal cell cancer. There remains much to learn, but the future is bright for anti-AXL therapies, though effective combinations and their impact may not be realized for years to come.

UR - http://www.scopus.com/inward/record.url?scp=85020815378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020815378&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-17-0189

DO - 10.1158/1078-0432.CCR-17-0189

M3 - Article

C2 - 28289089

AN - SCOPUS:85020815378

VL - 23

SP - 2928

EP - 2933

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 12

ER -