• An insight to immunotherapy methods and its challenges
  • Nora Arabbaraghi,1 Saman Hakimian,2,*
    1. Department of Cellular & Molecular Biology, Faculty of Advance Science & Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran
    2. Department of Microbiology, Faculty of Advance Science & Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran


  • Introduction: So far, cancer treatments such as surgery, chemotherapy, and radiotherapy have been utilized to remove or directly attack cancer cells. However, these treatments are often ineffective for advanced or recurrent stages of cancer. To address this, cancer immunotherapy has been proposed as the fourth cancer treatment. This type of therapy includes monoclonal antibodies, immune checkpoint blockers, cancer vaccines, and cell-based therapies, which have proven to be effective. While immunotherapies have revolutionized the future of treatment for various solid and hematologic malignancies, they also present unique toxicity profiles that vary depending on the type of immunotherapy used. Recent clinical studies have revealed that patients who respond to immunotherapy have longer survival rates with less metastatic recurrence, indicating that immunotherapy may be a solution to overcome cancer metastasis. However, there are limitations and challenges associated with this method of treatment. In this article, we will explore the different types of immunotherapy mentioned above and the obstacles of this type of cancer treatment. ICIs are monoclonal IgG antibodies that work by interrupting inhibitory signals that deactivate cellular immune effector cells. Immune checkpoints play a role in limiting the immune response and promoting self-tolerance by deactivating cytotoxic T-cells. By disrupting the interaction between immune checkpoints and cancer cells, ICIs keep T-cells activated and enable them to target cancer cells. Ipilimumab was the first immune checkpoint inhibitor (ICI) to be approved by the FDA in 2011 for the treatment of advanced melanoma. Clinical trials for multiple types of cancer have demonstrated that checkpoint inhibitors have favorable outcomes in both tumor regression and patient survival. However, non-specific immunostimulation caused by ICIs may lead to organ-specific inflammation, tissue damage, and autoimmunity, resulting in unique adverse effects.
  • Methods: The use of immune checkpoint inhibitors in clinical practice has significantly progressed cancer treatment. Nevertheless, their efficacy is restricted as tumor cells employ diverse mechanisms to evade antitumor effects. To overcome these mechanisms and enhance the adaptability of current cancer immunotherapies, it is crucial to gain a more comprehensive understanding of the TME and devise innovative approaches, such as cancer vaccines. We anticipate that this review will encourage further advancements in cancer immunotherapies One vaccine strategy being examined is an autologous tumor cell vaccine that employs a patient's cancer cells. This approach involves administering irradiated tumor cells with an adjuvant. Since this vaccine utilizes tumor cells, it has the potential to generate T cells that are specific to any antigen expressed by the cells used. However, the challenge with this strategy is that obtaining a sufficient number of cells can be difficult. This method has been tested in numerous tumors, including lung cancer, colorectal cancer, melanoma, renal cell carcinoma, and prostate cancer. Within the tumor microenvironment (TME), various cytokines are necessary for immune cells to sustain their growth, activation, and ability to infiltrate tumor regions. Specifically, administering IL-2 has demonstrated notable antitumor effects and reduced metastatic tumor progression in murine tumor models. In 1992, the FDA approved IL-2 therapy for the treatment of renal cell carcinoma and melanoma, with response rates ranging from 15% to 29% across different studies.
  • Results: Successful anti-cancer immune response requires multiple processes that are often compromised during tumor progression. Single-agent immunotherapy has limitations, and combining it with different steps of immunosurveillance may restore anti-tumor immunity. Defining immune profiles using biomarkers may reveal more efficient combination therapies. Current and future immuno-oncology will expand the frontiers of immunotherapy and benefit more cancer patients.
  • Conclusion: Immunotherapy has demonstrated encouraging outcomes in treating resistant cancer histologies. Despite this, its advantages are still constrained due to low response rates in certain tumor types and variations in response among different tumor lesions. Resistance to immunotherapy can arise from a variety of factors, including genetics, metabolism, inflammation, and abnormal neovascularization. Research is being conducted to identify and comprehend these mechanisms of resistance in order to enhance cancer diagnosis and treatment for personalized care. Harnessing and renormalizing immune responses in cancer patients has led to new cancer immunotherapies.
  • Keywords: Immunotherapy, immune checkpoint inhibitor, cancer vaccine