Immunotherapy for colorectal cancer: where are we heading?

Abstract

In the last few years, significant advances in molecular biology have provided new therapeutic options for colorectal cancer (CRC). The development of new drugs that target the immune response to cancer cells seems very promising and has already been established for other tumor types. In particular, the use of immune checkpoint inhibitors seems to be an encouraging immunotherapeutic strategy. Areas covered: In this review, the authors provide an update of the current evidence related to this topic, though most immunotherapies are still in early-phase clinical trials for CRC. To understand the key role of immunotherapy in CRC, the authors discuss the delicate balance between immune-stimulating and immune-suppressive networks that occur in the tumor microenvironment. Expert opinion: Modulation of the immune system through checkpoint inhibition is an emerging approach in CRC therapy. Nevertheless, selection criteria that could enable the identification of patients who may benefit from these agents are necessary. Furthermore, potential prognostic and predictive immune biomarkers based on immune and molecular classifications have been proposed. As expected, additional studies are required to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and enhance effector response.

Strategy to targeting the immune resistance and novel therapy in colorectal cancer

“…The crosstalk between NK and DCs might be a crucial point in the regulation of the whole immune defense against tumors and viruses [1,[179][180][181]. Accumulating evidences have indicated that the cytokine-producing Th cell capacity, Th cell polarization, as well as migration and stimulatory functions of DCs, could be regulated by activated NK cells [182,183].…”

“…This suggests that the association of COX inhibitors and immune checkpoint blockers could enhance the efficacy of immunotherapy and prevent resistance development. [1,126] Photodynamic Therapy in Combination with CTLA-4 blockade UCNP-Ce6-R837-based PDT combined with CTLA-4 blockade PDT treatment has the ability to activate the tumor-specific immune responses by producing tumor-associated antigens from tumor cell residues, which afterward may be processed by APCs such as DCs and then presented to T cells. PDT combined with CTLA-4 blockade would effectively induce the generation of TEM-based immune memory response to prevent tumor relapse.…”

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

“…CRC cells could acquire genetic alterations which in turn lead to escape from immune surveillance and resistance to immunotherapeutic treatments. This process can cause primary or acquired resistance in some patients (Basile et al, 2017). The marked upregulation of immunosuppressive factors that are important characteristics for CRC subtypes can be considered as a promising target for chemopreventive and/or chemotherapeutic strategies against CRC development and progression (Gang et al, 2018).…”

Recent Considerations in the Application of RAPTA‐C for Cancer Treatment and Perspectives for Its Combination with Immunotherapies

“…[146] It is certain that RAPTA compounds do not induce the cancer immune response via thioredoxin levels and the regulation of the activity of thioredoxin reductase. [147][148][149][150][151][152] Platinum-based drugs lead to an enhancement of the immune response directly at the tumor site, and therefore, it is very possible that certain ruthenium compounds will harbor similar properties. [147][148][149][150][151][152] Platinum-based drugs lead to an enhancement of the immune response directly at the tumor site, and therefore, it is very possible that certain ruthenium compounds will harbor similar properties.…”