Targeting the immune milieu in gastrointestinal cancers

Abstract

Gastrointestinal (GI) cancers are among the most common and lethal solid tumors worldwide. Unlike in malignancies such as lung, renal and skin cancers, the activity of immunotherapeutic agents in GI cancers has, on the whole, been much less remarkable and do not apply to the majority. Furthermore, while incremental progress has been made and approvals for use of immune checkpoint inhibitors (ICIs) in specific subsets of patients with GI cancers are coming through, in a population of ‘all-comers’, it is frequently unclear as to who may benefit most due to the relative lack of reliable predictive biomarkers. For most patients with newly diagnosed advanced or metastatic GI cancer, the mainstay of treatment still involves chemotherapy and/or a targeted agent however, beyond the second-line this paradigm confers minimal patient benefit. Thus, current research efforts are concentrating on broadening the applicability of ICIs in GI cancers by combining them with agents designed to beneficially remodel the tumor microenvironment (TME) for more effective anti-cancer immunity with intention of improving patient outcomes. This review will discuss the currently approved ICIs available for the treatment of GI cancers, the strategies underway focusing on combining ICIs with agents that target the TME and touch on recent progress toward identification of predictors of sensitivity to immune checkpoint blockade in GI cancers.

Prognostic importance of the preoperative New‐Naples prognostic score for patients with gastric cancer

“…Additionally, the difference in the concentration of interleukin 7 (IL‐7) secreted by immune cells in the TME between GC and CRC (GC vs CRC: 61.6 pg/g vs. 88.6 pg/g) has been reported to be correlated with the digestive tract flora 16 . Therefore, the difference in the digestive tract flora may be one of the reasons for the difference between the two in TME immunity 14,17 . In addition, tumor cells in the TME will cause different degrees of immune activation in the peripheral blood, leading to different degrees of inflammatory response in the body.…”

“… 16 Therefore, the difference in the digestive tract flora may be one of the reasons for the difference between the two in TME immunity. 14 , 17 In addition, tumor cells in the TME will cause different degrees of immune activation in the peripheral blood, leading to different degrees of inflammatory response in the body. Previous study found that the cutoff value of systemic immune‐inflammation index (SII) of CRC is different from that of GC (460.66 vs 660).…”

The role of myeloid‐derived suppressor cells in gastrointestinal cancer

“…This will likely clarify some unsolved aspects of the interaction between MDSCs and GI cancer cells, laying the groundwork for more effective therapeutic strategies in the future. Finally, unlike in malignancies such as lung, renal, and skin cancers, the efficacy of immunotherapeutic agents on GI cancer has, on the whole, been much less remarkable and do not apply to the majority [166]. This could be explained by the permeated MDSCs in the tumor microenvironment, which eliminated the response of activated T cells generated by PD1/PD‐L1 blockade.…”

Natural cell based biomimetic cellular transformers for targeted therapy of digestive system cancer

“…However, chemotherapeutic drugs often have disadvantages such as poor water solubility, low tumor targeting ability, and severe adverse reactions, which greatly limit their clinical applications [3]. At the same time, because most cases are found in the late stage of the disease, the effective treatment methods are very limited, resulting in a high fatality rate [4][5][6][7]. Therefore, exploring new therapeutic methods for digestive system cancer has become a hotspot of current research.…”