Biomarkers for response to immune checkpoint inhibitors in gastrointestinal cancers

Abstract

Gastrointestinal (GI) cancers account for a large proportion of cancer deaths worldwide and pose a major public health challenge. Immunotherapy is considered to be one of the prominent and successful approaches in cancer treatment in recent years. Among them, immune checkpoint inhibitor (ICI) therapy, has received widespread attention, and many clinical findings support the feasibility of ICIs, with sustained responses and significantly prolonged lifespan observed in a wide range of tumors. However, patients treated with ICIs have not fully benefited, and therefore, the identification and development of biomarkers for predicting ICI treatment response have received further attention and exploration. From tumor genome to molecular interactions in the tumor microenvironment, and further expanding to circulating biomarkers and patient characteristics, the exploration of biomarkers is evolving with high-throughput sequencing as well as bioinformatics. More large-scale prospective and specific studies are needed to explore biomarkers in GI cancers. In this review, we summarize the known biomarkers used in ICI therapy for GI tumors. In addition, some ICI biomarkers applied to other tumors are included to provide insights and further validation for GI tumors. Moreover, we present single-cell analysis and machine learning approaches that have emerged in recent years. Although there are no clear applications yet, it can be expected that these techniques will play an important role in the application of biomarker prediction.

Immunotherapy for esophageal cancer: Where are we now and where can we go

“…Several scoring systems such as CPS and TPS have been established, however, the ideal scoring system is not yet revealed, and biomarkers to select individual ICIs remain unknown. Recently, novel biomarkers to predict the treatment response and prognosis after ICI therapy such as tumor-genome biomarkers, tumor immune microenvironment-related biomarkers, and liquid biopsy biomarkers have been reported in several gastrointestinal diseases[ 24 ], and the combination of several biomarkers is noteworthy. Future prospective trials and the development of novel technologies, such as single-cell analysis and machine learning, may lead to the development of optimal ICI biomarker.…”

An inflammation‐associated ferroptosis signature optimizes the diagnosis, prognosis evaluation and immunotherapy options in hepatocellular carcinoma

“…Inflammation‐induced ferroptosis is favourable for cancer therapy, while the products of cells undergoing ferroptosis can act as immunogen to induce immune cell infiltration 22 . Previous studies indicated that ICI based on the data obtaining from high‐throughput sequencing is helpful for the precise treatment of HCC 23,24 . Herein, therefore, we first aimed to explore novel biomarker associated with inflammation and ferroptosis in HCC tissues, and its effect on guiding immunotherapy via analysing high‐throughput sequencing data.…”

“… 22 Previous studies indicated that ICI based on the data obtaining from high‐throughput sequencing is helpful for the precise treatment of HCC. 23 , 24 Herein, therefore, we first aimed to explore novel biomarker associated with inflammation and ferroptosis in HCC tissues, and its effect on guiding immunotherapy via analysing high‐throughput sequencing data.…”

Efficacy of immunotherapy in advanced gastric cancer: preliminary results of a multicenter observational study

“…Внедрение ингибиторов контрольных иммунных точек в рутинную клиническую практику позволило сохранить качество жизни пациентов, и в ряде исследований улучшить отдаленные результаты лечения в определенных группах пациентов с мРЖ [2, [10][11][12]. Так, наиболее хорошо изученными предикторами ответа на иммунотерапию являются уровень экспрессии PD-L CPS и наличие микросателлитной нестабильности (MSI) [13,14]. Стандартом первой линии мРЖ является комбинация ниволумаба или пембролизумаба с оксалиплатин-содержащими режимами при уровне PD-L CPS ≥5 и ≥10 соответственно [2,15].…”