Protagonist of Immuno-Profiling, Immuno-Scoring, and Immunotherapy Towards Colitis-Associated Cancer: Systematic Review

Introduction

The chronic inflammation in the large intestinal epithelial to rectum is a major risk for the malignancies. The pathogenesis of colitis associated cancer is distinct with perilous molecular mechanism. The inflammation leads to damage of cells resulting in symptomatic conditions including cancer. This suggest the relationship between certain cancer and the ulcerative colitis due to its various factors such as environment, genetics and chronic inflammation leading to cancer. Colorectal cancer (CRC), also acknowledged as bowel cancer, rectal or colon cancer. The most common types of adenocarcinomas are associated with colorectal cancer, the adenocarcinomas form mucus within the cells. The lymphomas, carcinoids, sarcoma and gastrointestinal tumors are also associated with CRC. Genetic mutations also associate in development of cancer forming polyps. The CRC are mostly found with polyp by creating and establishing internal mass of cells on the linings. The inflammatory bowel disease with chronic inflammation also results in the development of gastrointestinal malignancies but the pathogenicity behind the mechanism of formation of malignancies is unknown. Most disorders with chronic inflammation and exposure of immunosuppressant have an increased risk with the development of cancer leading towards the treatment of cancer by various therapies like radiation therapy, chemotherapy, hormonal therapy and further into immunotherapy. About 1.8 million cases of new colorectal cancer and about 881,000 deaths are estimated to occur in 2018 by colorectal cancer. The pathogenesis of colitis associated cancer is distinctive towards sporadic colorectal carcinoma. Moreover patients with CRC have found to develop metastasis during their lifetime. Hence the development of effective treatment is critical and treatment towards modulation of own immune system towards destroying cancers could be a viable treatment for the cancers by using checkpoint inhibitors and other immunotherapy.

The classification of tumor progression by TNM classification established by American joint committee on cancer is the most common classification method for evaluating the malignancies is often inadequate because the cancer patients with the histological same stages of tumors have been found to demonstration various clinical outcomes. The important part of tumor microenvironment and its immune environment has become a pivotal role towards the integral component for immunotherapy for the therapy of cancer. Medical therapies that weaken the immune system with increased inflammatory response have been found with evidences supporting their disease progression with outcome. However immune therapies altering the immune system are also been evidenced to promote the carcinogenesis with chronic inflammation. Diseases such as ulcerative colitis, crohn’s disease and other diseases have been evidenced with immune mediated disorders leading with chronic intestinal inflammation supporting towards gastrointestinal malignancy such as colorectal cancer, small bowel adenocarcinoma, gastrointestinal lymphoma, anal cancer, cholangiocarcinoma. The risk of the disease progression and outcome is highly inflammation associated, moreover the mutations by DNA methylation, aneuploidy, adenomatous polyposis coli (APC) gene mutation, activation of k-ras oncogene and COX-2, mutation in tumor suppressor gene DPC4, loss of p53 function and other associated factors like transcription factors, DNA mismatch repair and DNA base excision repair, signalling proteins leads into genomic changes. Even though clear reason is unknown oxidative stress is highly involved with ROS produced by the inflammatory cells. Mouse models have also been shown that with inflammation they are genetically prone to develop CRC with bacterial colonization. Adaptive and innate immune responses with these machineries and system are found to be associated with the formation of cancer.