Abstract
Immune checkpoint inhibitors (ICPis) have revolutionized cancer therapy with broad activities against a wide range of malignancies. However, in many malignancies their efficacy remains limited due to the primary resistance. Furthermore, a high percentage of patients develop progression due to the secondary resistance even after obtaining a response or achieving a stable disease. In this review, we will discuss the mechanisms that underlie the primary and secondary resistance to ICPis in cancer immunotherapy and provide an overview to impart a broad understanding of the critical issues that are encountered in clinical oncology practice.
Highlights
Immune checkpoint inhibitors (ICPis) have demonstrated a response rate ranging from approximately 80% for refractory Hodgkin lymphoma to less than 20% for most of the other malignancies
In our study of patients with metastatic melanoma treated with nivolumab or pembrolizumab, we observed that poor performance status (PS) and comorbidities were associated with a more rapid progression of disease [21]
Our data are consistent with a recent meta-analysis that included studies of patients with metastatic melanoma, non-small cell lung cancer, and urothelial carcinoma and showed that a high neutrophil-to-lymphocyte ratio (NLR) was associated with twice the risk of mortality and progression during treatment with ICPis [25]
Summary
Immune checkpoint inhibitors (ICPis) have demonstrated a response rate ranging from approximately 80% for refractory Hodgkin lymphoma to less than 20% for most of the other malignancies. For several types of cancer, the response rate has been in the single-digit range or only occasionally observed. Numerous factors impact the efficacy of the ICPis in cancer treatment [1,2]. These factors can be categorically divided into either the host or the tumor factors. We provide a review of the factors that are related to primary or secondary resistance to ICPis and discuss their potential mechanisms. Understanding these factors may provide important insight for guiding clinical practice and further research on cancer immunotherapy
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