Immunotherapy of Metastatic Colorectal Cancer: Prevailing Challenges and New Perspectives

Abstract

Patients with recurring or metastatic colorectal cancer (mCRC) have strikingly low long-term survival, while conventional treatments such as chemotherapeutic intervention and radiation therapy marginally improve longevity. Although, many factors involving immunosurveillance and immunosuppression were recently validated as important for patient prognosis and care, a multitude of experimental immunotherapies designed to combat unresectable mCRC have, in few cases, successfully mobilized antitumor immune cells against malignancies, nor conclusively or consistently granted protection, complete remission, and/or stable disease from immunotherapy – of which benefit less than 10% of those receiving therapy. After decades of progress, however, new insights into the mechanisms of immunosuppression, tolerance, and mutation profiling established novel therapies that circumvent these immunological barriers. This review underlines the most exciting methods to date that manipulate immune cells to curb mCRC, including adoptive cell therapy, dendritic cell vaccines, and checkpoint inhibitor antibodies – of which hint at effective and enduring protection against disease progression and undetected micrometastases.

Correlation of Blood T-Cells to Intratumoural Density and Location of CD3+ and CD8+ T-Cells in Colorectal Cancer

“…Furthermore, escape from immune surveillance is regarded as a cancer hallmark (3). Therefore, the understanding of how cancer cells avoid detection by the immune system is a research field of great interest, with new promising immunotherapy cancer treatments having been developed and under development (4,5).…”

Checkpoint immunotherapy: good for cancer therapy, bad for rheumatic diseases

“…The study of knockout models reveals that absence of CTLA4 is associated with a highly lethal and rapidly progressive lymphoproliferative and autoimmune disorder 9. In a spontaneous model of myasthenia gravis anti-CTLA4 has been documented to accelerate the autoimmune disease10 and in humans anti-CTLA4 associated hypophysitis is associated with anti-pituitary antibodies believed to mediate gland destruction 10. Genetic knockouts of PD-1 produce a milder autoimmune diathesis; in addition, at least one strain of mouse develops a lupus-like diathesis when PD-1 is genetically disrupted 11.…”

Identification of most influential co-occurring gene suites for gastrointestinal cancer using biomedical literature mining and graph-based influence maximization

“…3Step 3: From the sorted list, choose the node from the top (node with the highest influence) to be a seed node. (4) Step 4: Among the nodes that are not in the set of seed nodes, for each one of them compute the combined influence of the set of seed nodes on the other nodes. Sort these nodes based on the influence value.…”

“…Approximately 25% of GI cancers are diagnosed in an advanced stage, whereas another 25 to 50% of patients will develop metastases during the course of the disease [3]. GI cancers are still a leading cause of cancer death [4]. Therefore, it is imperative to explore potential effective influential genes to increase the number of patients qualified for curative treatments.…”