Harnessing the innate immune system and local immunological microenvironment to treat colorectal cancer

Abstract

Significant progress in the development of new immunotherapies has led to successful clinical trials for malignant melanoma and non-small cell lung cancer; however, for the majority of solid tumours of the gastrointestinal tract, little or no progress has been seen. The efficacy of immunotherapies is limited by the complexities of a diverse set of immune cells, and interactions between the tumour cells and all other cells in the local microenvironment of solid tumours. A large fraction of immune cells present in and around solid tumours derive from the innate arm of the immune system and using these cells against tumours offers an alternative immunotherapeutic option, especially as current strategies largely harness the adaptive arm of the immune system. This option is currently being investigated and attempts at using the innate immune system for gastrointestinal cancers are showing initial results. Several important factors, including cytokines, chemotherapeutics and the microbiome, influence the plasticity and functionality of innate (myeloid) cells in the microenvironment, and this complexity of regulation has limited translation into successful trials so far. In this review, current concepts of the immunobiology of the innate arm in the tumour microenvironment are presented in the context of clinical translation.

CCR5 status and metastatic progression in colorectal cancer

“…13 Therefore, either prevention of the metastatic stage or expanded therapeuticespecially immunotherapeuticoptions, are in the focus of current research. 39 Our histological analysis of primary tumors showed an even distribution of CCR5 expression across the whole tissue sections, without predominance in invasive parts of the tumor, and is in accordance to previously published studies: CCR5 was expressed by cancer cells, 40,41 by tumor-infiltrating lymphocytes 32 as well as by macrophages. 18 We additionally illustrate that CCR5 expression levels increase during primary tumor growth and peak in liver metastases, corroborating the hypothesis that CCR5 promotes metastasis.…”

OTUB1 Recruits Tumor Infiltrating Lymphocytes and Is a Prognostic Marker in Digestive Cancers

“…Although the prognosis of gastrointestinal tumors has been significantly improved by comprehensive treatments, the prognosis of patients with advanced gastrointestinal tumors is still unsatisfactory, meaning that further exploration of the prognostic value and immunoregulatory function of OTUB1 for digestive cancers is required. Immunotherapy plays a prominent role in tumor treatment, and digestive tumors may benefit from treatments related to immunotherapy (Kather and Halama, 2019). The type and level of tumor-infiltrating lymphocytes can affect the prognosis of the tumor and the efficacy of immunotherapy (Kather and Halama, 2019;Rohaan et al, 2019).…”

“…Immunotherapy plays a prominent role in tumor treatment, and digestive tumors may benefit from treatments related to immunotherapy (Kather and Halama, 2019). The type and level of tumor-infiltrating lymphocytes can affect the prognosis of the tumor and the efficacy of immunotherapy (Kather and Halama, 2019;Rohaan et al, 2019). OTUB1 is an important regulator in the level and types of tumor-infiltrating immunocytes.…”

Long non-coding RNA AGER-1 inhibits colorectal cancer progression through sponging miR-182

“…36 Cells of the innate immune system can be the primary effector in this inflammatory process, including persistent infections and sterile inflammation. 37 While AGER is expressed in innate immune cells, it has enabled the recognition of allergens and thus activated innate immune responses. Together, the host's own immune system may eradicate the tumor cells that rooted in the continuous inflammatory signals.…”