About this Research Topic
Rapid progress has been made in the development of immune checkpoint inhibitors (ICIs) as an effective treatment for non-small cell lung cancer (NSCLC), colon cancer and esophageal cancer. ICIs targeting programmed cell death-1 (PD-1) and PD-L1, such as Nivolumab, Atezolizumab, and Pembrolizumab, have been used in the first line treatment for advanced NSCLC, either as monotherapy, or in combination with other immunotherapy drugs or chemotherapy. The five-year survival rate of patients treated with ICIs varies from person to person and also depends on the subtypes of tumor. For example, ICIs have proved to be quite effective in treatment of mismatch repair deficient and microsatellite instability high colon tumors, but it has either been unsuccessful when used in other subtypes, or not extensively explored.
The efficacy of ICIs is limited by resistance which is associated with immune metabolic dysregulation. About 70 % of patients are classified as non-responders to ICIs, or they progress after initial response to these ICIs. Immunotherapy resistance is due to a combination of factors, such as immune escape, the decrease of anti-tumor T lymphocytes and increased extracellular adenosine. In addition, immune-tolerant tumor microenvironment caused by immunotherapy may lead to immune-related adverse events, affecting several organs or systems and even leading to termination of treatment.
At a result, the factors for ICIs immunotherapy that can predict the response or resistance of cancer patients is very important. For NSCLC and colon cancer, PD-L1 expression by immunohistochemistry is now recognized as an effective biomarker to predict the appreciate response to ICIs. But some patients with highly positive PD-L1 do not show response. PD-1 expression is still unperfect to establish effective treatment strategies. Better and more predictive factors are needed for more accurate patient selection for ICI treatment in NSCLC, colon cancer and esophageal cancer.
This Research Topic aims to provide a forum to update and discuss the new discoveries in the field of immunotherapy with immune checkpoint inhibitors in non-small cell lung cancer, colon cancer and esophageal cancer.
We welcome submissions of Original Research, Review, and Mini Review focusing on major trends and challenges in this field, including but not limited to:
● Novel findings on the mechanisms underlying resistance to ICIs (eg. impaired HLA Class I Antigen processing);
● New preclinical or clinical studies on the combination of ICIs in treatment of cancers;
● Discovery and validation of new biomarkers to predict the therapeutic efficacy of PD-1 (eg. the application of antigenicity, regulatory molecules on cancer or cancer steam cells in the treatment of colon cancer);
● The changes in the tumor microenvironment and their impact on patients’ response to immunotherapy with ICIs (eg. increase of tumor-infiltrating immune cells is often described as being capable of turning immunologically “cold” tumors into “hot” ones).
Keywords: NSCLC, immunotherapy, checkpoint inhibitor, colon cancer, esophageal cancer, combination therapy
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