Circulating immune cell dynamics as outcome predictors for immunotherapy in non-small cell lung cancer

Abstract

The use of immune checkpoint inhibitors (ICIs) continues to transform the therapeutic landscape of non-small cell lung cancer (NSCLC), with these drugs now being evaluated at every stage of the disease. In contrast to these advances, little progress has been made with respect to reliable predictive biomarkers that can inform clinicians on therapeutic efficacy. All current biomarkers for outcome prediction, including PD-L1, tumor mutational burden or complex immune gene expression signatures, require access to tumor tissue. Besides the invasive nature of the sampling procedure, other disadvantages of tumor tissue biopsies are the inability to capture the complete spatial heterogeneity of the tumor and the difficulty to perform longitudinal follow-up on treatment. A concept emerges in which systemic immune events developing at a distance from the tumor reflect local response or resistance to immunotherapy. The importance of this cancer ‘macroenvironment’, which can be deciphered by comprehensive analysis of peripheral blood immune cell subsets, has been demonstrated in several cutting-edge preclinical reports, and is corroborated by intriguing data emerging from ICI-treated patients. In this review, we will provide the biological rationale underlying the potential of blood immune cell-based biomarkers in guiding treatment decision in immunotherapy-eligible NSCLC patients. Finally, we will describe new techniques that will facilitate the discovery of more immune cell subpopulations with potential to become predictive biomarkers, and reflect on ways and the remaining challenges to bring this type of analysis to the routine clinical care in the near future.

Characterization of unique pattern of immune cell profile in patients with nasopharyngeal carcinoma through flow cytometry and machine learning

“… 23 , 24 For example, in non‐small‐cell lung cancer, immune cell profile alterations are believed to be a promising biomarker for predicting clinical responses to ICI immunotherapy. 25 Although previous studies have well‐documented the features of immune cell profile in the tumour microenvironment of NPC, 26 , 27 , 28 characterization of circulating immune cell profiling remains unclear. In this study, we examined the requirements of circulating immune cell profiling in patients with NPC and provided comprehensive treatment‐related information.…”

“…Adjustment of the profile of circulating immune cells is well‐documented in various types of cancer 23,24 . For example, in non‐small‐cell lung cancer, immune cell profile alterations are believed to be a promising biomarker for predicting clinical responses to ICI immunotherapy 25 . Although previous studies have well‐documented the features of immune cell profile in the tumour microenvironment of NPC, 26–28 characterization of circulating immune cell profiling remains unclear.…”

New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication

“…Thus, circular immune cell‐based biomarkers can assess and provide guidance for cancer immunotherapy. 246 Liquid biopsies can be used to assess the progression of tumors and the efficacy of clinical therapies during cancer immunotherapy. Among them, ctDNA could be used as a tumor load biomarker to assess the efficacy of immunotherapies.…”

An organoid co-culture model for probing systemic anti-tumor immunity in lung cancer

“…A series of characteristics of tumors have been utilized as predictive biomarkers for ICI responses, such as PD-L1 expression of tumor cells, T cell infiltration into tumor tissues, tumor mutation burden, etc. 5 Unfortunately, none of these indices have been proven trustworthy at all time, due mainly to the complex interactions between tumor and the macro-environment of the host body. The anti-tumor immunity is coordinated across tissues, and the localized anti-tumor immune response cannot persist without continuous communication with the peripheral immune cells.…”