PD-1 and PD-L1 inhibitors in cold colorectal cancer: challenges and strategies. Cancer Immunol Immunother 2023 Dec;72(12):3875-3893
Date
10/13/2023Pubmed ID
37831146Pubmed Central ID
PMC10700246DOI
10.1007/s00262-023-03520-5Scopus ID
2-s2.0-85174215652 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Colorectal cancer (CRC) is the second most common cause of cancer mortality, with mismatch repair proficient (pMMR) and/or microsatellite stable (MSS) CRC making up more than 80% of metastatic CRC. Programmed death-ligand 1 (PD-L1) and programmed death 1 (PD-1) immune checkpoint inhibitors (ICIs) are approved as monotherapy in many cancers including a subset of advanced or metastatic colorectal cancer (CRC) with deficiency in mismatch repair (dMMR) and/or high microsatellite instability (MSI-H). However, proficient mismatch repair and microsatellite stable (pMMR/MSS) cold CRCs have not shown clinical response to ICIs alone. To potentiate the anti-tumor response of PD-L1/PD-1 inhibitors in patients with MSS cold cancer, combination strategies currently being investigated include dual ICI, and PD-L1/PD-1 inhibitors in combination with chemotherapy, radiotherapy, vascular endothelial growth factor (VEGF) /VEGF receptor (VEGFR) inhibitors, mitogen-activated protein kinase (MEK) inhibitors, and signal transducer and activation of transcription 3 (STAT3) inhibitors. This paper will review the mechanisms of PD-1/PD-L1 ICI resistance in pMMR/MSS CRC and potential combination strategies to overcome this resistance, summarize the published clinical experience with different combination therapies, and make recommendations for future avenues of research.
Author List
Lin KX, Istl AC, Quan D, Skaro A, Tang E, Zheng XAuthor
Alexandra C. Istl MD, MPH Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
B7-H1 AntigenColonic Neoplasms
Colorectal Neoplasms
Humans
Microsatellite Instability
Programmed Cell Death 1 Receptor
Rectal Neoplasms
Vascular Endothelial Growth Factor A