Journal of Mucosal Immunology Research
Open Access

Colorectal cancer; Immunotherapy; Checkpoint blockade; Mismatch repair; Neoantigens; Tumor infiltrating lymphocytes; Cancer stem cells; Tumor microenvironment.

Introduction

When aberrant cells proliferate and spread throughout the human body, cancer is created. Cancer cells differ from normal cells in two distinct ways: they grow out of control and spread throughout the body. Eight characteristics, including maintaining proliferative signalling, dodging growth inhibitors, resisting cell death, enabling replicative immortality, inciting angiogenesis, activating invasion and metastasis, reprogramming of energy metabolism, and dodging immune destruction, have been identified as hallmarks of cancer cells in recent studies. Typically, intrinsic or external causes that cause gene alterations lead to the development and proliferation of cancer cells. According to estimates, there will be 1.66 million new cases of cancer and 0.58 million cancer-related deaths in the United States in 2013. By 2030, it is anticipated that there will be 20–30 million new instances of cancer and 13–17 million cancer-related deaths worldwide. The world’s most severe health issue right now is cancer [1].

Both scientists and medical professionals still struggle with the challenge of treating cancer. Surgery, radiation, chemotherapy, hormone therapy, biological therapy, and targeted medicines are currently the most common cancer treatments. However, there is currently no effective approach for treating cancer. Immunotherapy is emerging as a novel, promising approach to treating cancer as the field of immunological science and allied fields continues to advance. The history, present state, and future of immunotherapy as a cancer treatment are covered in this essay.

A expanding area of study in immunology, cancer immunology examines the interactions between cancer cells and the immune system with the goal of identifying biomarkers for cancer immunodiagnosis and developing novel cancer immunotherapies. In the subject of cancer immunology, the immune response, particularly the detection and recognition of cancer-specific antigens, is of special interest because new vaccines and antibody treatments are being developed as a result of the knowledge obtained [2]. Immunooncology has long sought to activate the immune system for therapeutic effect against cancer. Since passive cancer immunotherapy has been around for a while, further developments in antibody and T-cell engineering should significantly increase its therapeutic effectiveness. The active cancer immunotherapy has shown to be difficult to implement in comparison to various passive immunotherapy techniques. These successes imply that active immunotherapy represents a route to achieving a long-lasting and durable response in cancer patients. This is especially true in light of recent developments in our understanding of how tolerance, immunity, and immunosuppression regulate antitumor immune responses as well as the introduction of targeted therapies. A better understanding of the immune response during cancer genesis and progression is essential for cancer immunodiagnosis and immunotherapy [3].

Globally, there is a lot of interest in the molecular and cellular interactions between cancer cells and the immune system. Accordingly, it is time to assess their potential as a stand-alone strategy or in combination with conventional cancer therapeutic modalities. Concurrently, with a better understanding of the complexities of cancer immunology, immunotherapeutic approaches to treat cancer have seen tremendous growth in recent years. Immunotherapeutic interventions for metastatic renal cell carcinoma (RCC) are described in detail in the thorough review by M. L. “Immunosuppression and Multiple Primary Malignancies in Kidney-Transplanted Patients: A Single-Institute Study,” as well as providing readers with the most recent information in the field. The body’s abnormal cells proliferate out of control, which leads to cancer [4]. The mechanisms behind the development of cancer, though, remain poorly understood. Early research has demonstrated that the genesis of cancer involves several steps. According to this theory, gene mutations cause two or more oncogenes to function in concert to cause a sequential succession of modifications that lead to the malignancy of normal cells. Prostate cancer, colorectal cancer, breast cancer, acute lymphoblastic leukaemia (ALL), acute myelogenous leukaemia (AML), and myeloproliferative diseases have all shown the multistep nature of cancer formation. Cancer development often involves several stages, including initiation, promotion, and progression. The multistep hypothesis of cancer development has implications for cancer treatment since it allows for the efficient interruption of early neoplastic cells before the emergence of malignant cells [5].

Numerous types of cancer are prevented from developing because the immune system is naturally able to recognise and eliminate aberrant cells. However, occasionally the immune system may fail to recognise and eliminate cancer cells. Cancer cells may express proteins on their surface that cause immune cells to be inactivated, cause cells in the microenvironment to release substances that suppress immune responses, decrease the expression of tumour antigens on their surface, making it more difficult for the immune system to detect them, and promote the proliferation and survival of tumour cells. The study of cancer immunology has made remarkable strides in recent years, resulting in a number of novel cancer patient treatment regimens that may strengthen the body’s defences against malignancies. Immunotherapies may be effective by enhancing the functions of particular immune system cells or by blocking the signals sent by cancer cells that inhibit immune responses. Huge, sustained investments in basic immune system research have enabled these advancements in cancer immunotherapy. However, the field of immunotherapy research is still very active. Understanding why immunotherapy is only helpful in a small percentage of cancer patients requires extensive additional research. It is necessary to identify the patients who will benefit most from an immunotherapy-based strategy by using prognostic and predictive biomarkers. Furthermore, on-going studies are concentrating on extending the application of immunotherapy to more cancer types [6]. The effectiveness of immunotherapy can be increased by combining it with other anticancer therapies like targeted therapy, chemotherapy, and radiation therapy as well as combinations of various immunotherapy agents. This is a crucial area of research. The US Food and Drug Administration (FDA) approved the first adoptive cell immunotherapy, known as chimeric antigen receptor (CAR) T-cell therapy, and gave a drug its first tissue/site-agnostic approval in the past year. Tissue/site-agnostic means that the treatment is effective against various cancer types that have a common genetic abnormality. Pembrolizumab has been authorised for use in adult and paediatric patients with locally advanced or metastatic solid tumours that are mismatch-repair deficient or have a high level of microsatellite instability (MSI-H), who have advanced following previous therapy and who lack an adequate alternative course of treatment. This illustrates the idea that a biomarker might better define the disease than the site and represents a paradigm shift in the approval of cancer medications [7].

Materials and Methods

From January 2019 until 2022, 100 hyperuricemia patients from Shandong, China’s Medical College of the Second Clinical College were chosen as the study’s participants. The randomization method (coin toss method) was used to divide them into groups A and B, each of which contained 50 patients. There were 28 males and 22 females in group A, who were all between the ages of 46 and 56 (mean years), and group B, who were all between the ages of 46 and 55. (Mean years). Both groups shared the same general information, which allowed for comparison. Fasting serum uric acid levels of >420 mol/L in men and menopausal women, or >357 mol/L in premenopausal women, were required for diagnosis [8].

The following were the inclusion requirements: I patients who withdrew from other clinical studies within a month of enrolment; (ii) patients who were not allergic to and tolerated the study’s drugs; (iii) all postmenopausal women; and (iv) patients’ family members and other participants in the study. Participants in the study who signed written information permission did so voluntarily.

The following were the exclusion requirements: I all patients with secondary HUA, including those with myeloma, leukaemia, polycystic kidney disease, renal failure, and certain endocrine diseases; (ii) people with mental illness who are unable to communicate; (iii) pregnant or nursing women; (iv) people with other critical organ dysfunctions; and (v) people who had undergone other treatments prior to enrolling in the study [9].

Discussion

It is now widely accepted that pyroptosis serves as a doubleedged sword in cancer patients due to its varied effects on tumour cell homeostasis, tumour immunity, and TME modulation. Growing evidence has implicated the vital and versatile roles of pyroptosis in a variety of cancers with different genetic backgrounds. A thorough investigation of pyroptosis in pan-cancer is therefore essential to pinpoint the precise role it plays in various tumours. It is also crucial to determine the cancer type-specific gene signature as a precise tool for predicting disease progression and patient prognosis since tumour cells react differently to various pyroptosis-based treatments [10].

In order to solve these problems, we first looked at whether the prognosis of various cancer types may be influenced by pyroptosis activity, as shown by the expression of 13 key genes. As anticipated, we found a connection between pyroptosis activity and the prognosis for 8 different cancer types. The associations, which we designated as PPRC and PNRC in Figures 2(a)–2(d), are diverse, with pyroptosis being positively connected with patient survival in some cancer types and adversely associated with patient survival in others. There might be untapped mechanisms connecting later discovered hub genes with pyroptosis-associated cancer prognosis, perhaps by tumour immunity related biological processes (Note: Later revealed hub genes are not directly engaged in pyroptosis signalling per se) [11]. (a) Shows that the signature is variably connected with immune cell infiltration in two cancer subtypes, and Figures 5(d) and 5(g) show that there is strong evidence that the signature can be used to predict the effectiveness of immunotherapy. The two batches of PPRC and PNRC signature genes were further validated as prognostic markers and a pathological stage indicator in patients from several public cancer databases, demonstrating their prognostic and predictive relevance in pyroptosisrelated cancer subtypes. These results suggested that the two batches of PPRC and PNRC signature genes might reflect different tumour immunity responses in different pyroptosis-related cancer subtypes [12].

Conclusion

The field of cancer immunotherapy has changed significantly in recent years, and it is now scientifically proven to be an efficient method of treating a variety of malignancies. Due to their ability to deliver significant amounts of patient-specific antigens derived from a small tumour sample, non-HLA restriction, induction of humoral and cellular immune responses, provision of costimulatory signals, lack of oncogenic potential, and good tolerability, RNA vaccines represent an appealing form of cancer immunotherapy. Several methods have been created to enhance IVT mRNA stability and translational effectiveness as well as to optimise RNA vaccine administration, as was covered in this review. Clinical responses to RNA vaccines are still low, despite these advancements [13].

Future research may improve treatment outcomes by combining RNA vaccines with additional medicines that have unique mechanisms of action. For instance, immune checkpoint inhibitors like anti- CTLA-4, anti-PD-1, and anti-PD-L1 could be employed in conjunction with the above-mentioned vaccination strategies either concurrently or sequentially. In such a combination therapy, immune checkpoint inhibition may be crucial in sustaining the immune responses and improving tumour cell clearance, while RNA vaccines may be significant in selectively targeting tumours, lowering tumour burden, and triggering tumour cell lysis and antigen spread [14].

In addition, just like antibodies against immune checkpoints, we explore the significance of RNA techniques to directly block immune checkpoints and tailor the tumour microenvironment in this study. These methods could perhaps reduce the toxicity and adverse effects related to the systemic administration of antibodies that block immunological checkpoints.

With the overarching objective of enhancing clinical outcomes and cancer care, additional research is required to explicitly examine combinations of RNA vaccines with other immunotherapies as well as targeted and cytotoxic medicines [15].

Acknowledgments

None

Conflict of Interests

None

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