Abstract Immunotherapy in the metastatic setting has drastically altered the landscape of treatment for various types of malignancy, including colorectal cancer. The category of immune checkpoint inhibitors has especially emerged as a class of therapy predicated on a more comprehensive understanding of immune cell-cancer cell regulation and evolution of the tumor microenvironment over time. Strategies including adoptive cellular therapies, tumor vaccines, and antibodies have also demonstrated ability to enhance antitumor immunity. In this article, we provide a comprehensive review of the current landscape of immunotherapeutic strategies in colorectal cancer and provide insight into how these strategies may evolve in the next decade and be adapted to more localized forms of cancers of the colon and rectum. We provide particular focus on various combination approaches under investigation for reversing cancer-induced immunosuppression, especially in mismatch repair proficient/microsatellite stable colorectal tumors. Finally, we summarize current understanding on a recently identified integral factor in local immune regulation, the colonic microbiome. The aim of this article is to identify current challenges and barriers to improvement, and to specify opportunities for applying knowledge in the immunotherapy sphere to rational design of clinical trials intended to improve survival and related outcomes in patients treated in the neoadjuvant setting.
#1Hyuna Sung(ACS: American Cancer Society)H-Index: 19
#2Jacques Ferlay(IARC: International Agency for Research on Cancer)H-Index: 77
Last. Freddie Bray(IARC: International Agency for Research on Cancer)H-Index: 119
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This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated ...
#2Karim Essani(WMU: Western Michigan University)H-Index: 14
Colorectal cancer is the third most common neoplasm in the world and the third leading cause of cancer-related deaths in the USA. A safer and more effective therapeutic intervention against this malignant carcinoma is called for given the limitations and toxicities associated with the currently available treatment modalities. Immuno-oncolytic or oncolytic virotherapy, the use of viruses to selectively or preferentially kill cancer cells, has emerged as a potential anticancer treatment modality. ...
Last. Ben Boursi(TAU: Tel Aviv University)H-Index: 12
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The gut microbiome has been shown to influence the response of tumors to anti-PD-1 immunotherapy in pre-clinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. Here we performed a phase I clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and re-induction of anti-PD-1 immunotherapy in ten patients with anti-PD-1-refractory metastatic melanoma. We obse...
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer deaths worldwide. Besides common therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, novel therapeutic approaches, including immunotherapy, have been an advent in CRC treatment. The immunotherapy approaches try to elicit patients` immune responses against tumor cells to eradicate the tumor. Monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T cells are two branches of...
PURPOSE Regorafenib is synergistic with immune-checkpoint inhibition in colorectal cancer pre-clinical models. EXPERIMENTAL DESIGN This is a single-arm, multicentric phase II trial. Regorafenib was given 3 weeks/4, 160mg QD; Avelumab 10 mg/kg IV was given every 2 weeks, beginning at C1D15 until progression or unacceptable toxicity. The primary endpoint was the confirmed objective response rate under treatment, as per RECIST 1.1. The secondary endpoints included: 1-year non-progression rate, prog...
Abstract Background Programmed death 1 (PD-1) blockade has clinical benefit in microsatellite-instability–high (MSI-H) or mismatch-repair–deficient (dMMR) tumors after previous therapy. The efficac...
Last. Akram Jalali(Hamedan University of Medical Sciences)H-Index: 4
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Cancer vaccines are usually derived from the patient's tumor cells or the antigens found on their surface, which may help the immune system to identify and kill these malignant cells. Current focus of many researches is designing vaccines with the hope of triggering the immune system to attack cancer cells in a more effective, reliable and safe manner. Although colorectal cancer (CRC) is recognized as the third leading cause of death by cancer, but significant advances in therapy strategies have...
The introduction of checkpoint inhibitors provided remarkable achievements in several solid tumors but only 5% of metastatic colorectal cancer (mCRC) patients, i.e., those with bearing microsatellite instable (MSI-high)/deficient DNA mismatch repair (dMMR) tumors, benefit from this approach. The favorable effect of immunotherapy in these patients has been postulated to be due to an increase in neoantigens due to their higher somatic mutational load, also associated with an abundant infiltration ...
Last. Khurum Khan(UCL: University College London)H-Index: 2
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Abstract Gastrointestinal cancers include colorectal, gastric, oesophageal, pancreatic and liver cancers. They continue to be a significant cause of mortality and morbidity worldwide. Current treatment strategies include chemotherapy, surgery, radiotherapy and targeted therapies. Immunotherapy has recently been incorporated in treatment regimens for some gastrointestinal malignancies and research into different immune modifying treatments is being carried out in this context. Approaches to immun...
Resiquimod (R848) and motolimod (VTX-2337) are second-generation experimental derivatives of imiquimod, an imidazoquinoline with immunostimulatory properties originally approved by the US Food and ...
