A. Immunotherapy

When it comes to treating brain tumors, immunotherapy is a potential treatment option. Chemotherapy, radiation treatment, and surgery have all been used to treat it in the past. An immune-based cancer therapy uses the body's immune system to destroy cancer cells [93]. If the cells are no longer required or pose a hazard, apoptosis, or programmed cell death, will occur to halt cell growth [94]. Cancer progresses and develops through eight processes, which are as follows:

1.Stained proliferation

2.Evasion of growth suppressor

3.Cell death resistance

4.Replicative immortality


7.Reprogrammed metabolism

8.Evasion of immune destruction [95].

The evasion of immune destruction has been studied for decades. Because EphA2 is abundantly expressed in glioblastoma but only at low levels in normal brain tissue, CAR T cell treatment targeting the glioblastoma antigen EphA2 is an appealing strategy to enhance outcomes [93].

Since brain tumor immunotherapy has been extensively studied [94–96], we will focus in this work on the most recent and late-stage clinical trial treatments, as well as the engineering problems these immunotherapies confront in the brain tumor environment [96].

i. Vaccines

Traditional vaccinations against viral illnesses (for example, influenza) employ attenuated or live viruses in combination with a danger signal (as an adjuvant) to activate DCs. DCS then takes up the viral antigen, digests it, moves to lymph nodes through lymphatic channels, and activates T-cells via the presentation of various peptide antigens/antigenic epitopes on MHC molecules [93].

a. Peptide vaccines

Immunization using peptide vaccine when released at the tumor site, peptide vaccinations stimulate T-cell responses by releasing antigen-specific peptides. APCs take up peptides, which are often associated with carrier proteins and adjuvants, and display them on the cell surface by way of MHC [97]. The treatment method by peptide vaccine is explained in **Figure 8**.

*An Overview of Brain Tumor DOI: http://dx.doi.org/10.5772/intechopen.100806*

**Figure 8.**

*Dendritic vaccine therapy and treatment method by peptide vaccine.*

APCs take up peptides, which are often associated with carrier proteins and adjuvants, and display them on the cell surface by way of MHC. Molecules of human leukocyte antigens (HLA) MHC I (HLA) [98].

b. Dendric cell vaccines

If you are looking for an alternative to peptide vaccines in situ, you may also use direct activation of DCs ex vivo to create a cancer vaccine. Autologous dendritic cells derived from peripheral blood monocytes primed with tumor-related antigens have been utilized in cancer immunotherapy instead of injecting a peptide that is given to an APC [99]. If there are inflammatory signals, immature CD4+ T cells can deliver antigen to T-cells that recognize it in an MHC-restricted way as a result of immature DC maturation. T-cells activated with CD8 + antigens and MHC I complexes may now identify tumor cells and seek to lyse them [100]. Dendritic vaccine therapy is explained in **Figure 8.**

ii. Adaptive cell therapy (ACT)

T-cells, x-cells, and other tumor infiltrating lymphocytes (TILs) can be activated directly via Adoptive Cell Therapy (ACT) instead of DC activation [101].

Adaptive cell therapy is shown in **Figure 9**. It is most usual to utilize cytokine-induced killer (CIK) and CAR T-cells in the ACT process.

**Figure 9.** *Adaptive cell therapy.*

> IFN, IL2, and CD3 monoclonal antibodies are used to induce peripheral blood lymphocytes into CIK cells in vitro. Cells that have been modified to express a single or many costimulatory tumor antigens are called CAR T-cells [102].

iii. Monoclonal antibodies

Using monoclonal antibodies is a passive method of immunotherapy that does not need the body's immune system. **Figure 10** shows the monoclonal antibodies treatment method [93]. Antibodies that target abnormally expressed surface receptors in malignancies or receptors implicated in carcinogenesis are generally selected. However, Nimotuzumab, another monoclonal antibody widely used in brain tumors, is an anti-EGFR inhibitor that has only slightly improved overall survival when administered in children with high-grade gliomas [103].

To some extent, monoclonal antibody treatment in the brain has suboptimal survival benefits because monoclonal antibodies are unable to penetrate the BBB without causing considerable barrier disruption and because patient-specific antigen mutations affect antibody binding efficiency [104].

iv. Virotherapy

Non-pathogenic viruses are used in oncolytic virotherapy to selectively infiltrate or express proteins in brain tumor cells that can directly destroy cancer cells or else activate an immune response. Many virotherapy techniques have been investigated, but their broad use in the brain remains a problem [105]. The virotherapy method for brain tumor treatment is shown in **Figure 11**.

*An Overview of Brain Tumor DOI: http://dx.doi.org/10.5772/intechopen.100806*

#### **Figure 10.**

*Monoclonal antibodies treatment method.*

Furthermore, the targeting of non-neuronal lineage cells may make a method like PVSRIPO appealing; nevertheless, other component cells in the CNS may be misidentified for cancer cells, resulting in negative side effects. The BBB can also limit viral migration to the tumor site, which is important in virotherapy for brain cancers [106].

B. Radiation therapy

Patients with primary brain tumors benefit from radiation therapy because it helps them maintain local control or prolong their progression-free life. In the treatment of primary brain tumors, radiation therapy (RT) plays a crucial role, with the majority of patients experiencing local control or prolonged progression-free survival. On the other hand, RT can have a negative

**Figure 11.** *Virotherapy method for brain tumor treatment.*

influence on cognitive performance, which can have a detrimental effect on the quality of life. When one or more cognitive processes, such as attention, memory, language, and executive function are impaired [107, 108].

Primary brain tumors, both benign and malignant, are commonly treated with radiation therapy (RT). Post-treatment neurocognitive deterioration has been documented with RT in verbal and visuospatial memory most commonly (i.e., difficulty encoding, retaining, and retrieving visual information) [109, 110].

#### C. Surgery

The majority of therapy is surgical resection. Patients with persistent hydrocephalus despite tumor excision require a third ventriculostomy or CSF diversion to cure the condition. A cardiac examination should be performed on neonates suspected of having tuberous sclerosis before an intraventricular tumor is surgically removed [111].

#### D.Chemotherapy

The discovery of chromosomal markers that indicate greater chemosensitivity in patients with low-grade astrocytoma and other histopathologies has sparked renewed interest in using chemotherapy in the treatment of lowgrade astrocytoma patients with other histopathologies. Temozolomide is the most widely used chemotherapy regimen in adult low-grade astrocytoma patients, followed by procarbazine, CCNU, and vincristine (PCV) if temozolomide fails [112].

The Southwest Oncology Group conducted an early randomized trial to see if treating low-grade astrocytoma patients with single-agent CCNU after radiation was beneficial. In this research, adding CCNU to the therapy schedule had no further benefits. Furthermore, individuals in the CCNU arm experienced a high rate of hematologic adverse effects after chemotherapy [113].

The effectiveness of temozolomide, an oral alkylating drug, in treating patients with low-grade astrocytoma is now a staple of adjuvant treatment, although it is also being investigated in several trials [114]. Response rates range from 31 to 61 percent when minor replies are considered. Despite the short duration of follow-up, the median time to advancement ranged from 31 months to >36 months. It was concluded by Brada and co-workers (2003, in a phase 2 study) that the drug temozolomide has single-agent action against low-grade astrocytoma and may also assist control seizures in this patient group and that it is safe and effective in this patient population [115].

#### **10. Recent research in brain tumor**

In 2020, A new improved WOA is used to propose a comprehensive method for brain tumor detection based on optimal feature extraction and feature selection. On a set of benchmark cases, IWOA's experimental results are compared to those of other common optimizers, and the results are verified [116].

Z.U. Rehman, M.S. Zia, G.R. Bojja, and F. Jinchao explained Two recent and useful trends for brain tumor localization: (1) using the texton-map to create the image in texture form (2) extracting the features from the superpixels The three contributions were used in this paper. First, superpixel segmentation is performed on texton-map images, which reduces the computational cost of image

#### *An Overview of Brain Tumor DOI: http://dx.doi.org/10.5772/intechopen.100806*

segmentation in small regions, improves spatial smoothness of superpixels, and improves low-level feature accuracy. Second, we covered the concept of data balancing, which aids in the development of vision-based classifiers. Third, we created a quick comparison of four different classifiers and examined their performance in terms of model training accuracy. Initially, our image denoising method is shown to effectively remove false-positive regions [117].

Ratan et al. developed watershed segmentation and used edge detection, contrast, and greyscale on 2D and 3D images to detect brain tumors. Somasundaram and Kalaiselvi used ten data sets with normal and abnormal subjects to detect brain tumors. Muscles, scalp, skull, and fats the unwanted brain areas are removed first in their proposed framework, followed by fuzzy segmentation. Finally, for tumor region detection, and intensity-based extended maxima transform is used [18]. proposes a systematic model that starts with a diagnosis of the brain tumor and then extracts the brain tumor region. A classifier called Naive Bayes is used to diagnose the tumor from brain MR images. After a diagnosis, the brain tumor region is extracted using K-mean clustering and boundary detection techniques. It had an accuracy rate of over 80%. To detect the brain tumor region, researchers propose a segmentation method based on color and edge detection. Edge detection is done with the Prewitt, Canny, Sobel, and Laplacian of Gaussian operators, while colorbased segmentation is done with the K-mean clustering technique [118].

Alexander Winkler-Schwartz and his colleagues have created a comprehensive research framework for studying oncological neurosurgery's technical performance and resection extent. This platform works by incorporating a low-cost alginatebased artificial brain tumor into an ex-vivo calf brain in a controlled operative environment. To our knowledge, this is the first time an artificial tumor has been created using the biomechanical properties of human specimens obtained through resection. Given that its components are relatively inexpensive and combined in small quantities, the overall cost of the artificial tumor is well under 2 cents/mL. To put this into perspective, 1 kg of alginate and 5800 mL of calcium sulphate, respectively, can yield 40,000 and 5800 mL of final tumor. Gadobutrol (Bayer AG) or its analogues, arguably the most expensive compound in the mix, can often be obtained for a low price from clinical units' expired stockpiles. Even if one were to pay the full cost for an average 30-mL vial, this would yield 27,000 mL of tumor. A 10e100-mL pipette and a laboratory-grade scale are required, but they are both onetime purchases. The recordings from the surgical microscope and ceiling-mounted camera, as well as the movements generated by the instrument-mounted fiducial markers, can be used to evaluate operative "performance" [119].

Medical imaging is still the gold standard for detecting, diagnosing, and examining gliomas and other diseases. Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI, computed tomography, and positron emission tomography is the most commonly used imaging techniques in clinical practice [120].

### **11. Discussion**

The brain is responsible to control all activities of the human body. It is wellknown that a disease occurred in the brain may affect human life negatively. A brain tumor is one of the critical diseases that originate from the abnormal growth of cells in the brain. Automatic brain tumor classification plays an important role in the early stage of tumor detection and this system allows patients to be diagnosed in time and chance of survival. Also, this system may help radiologists in decisionmaking and treatment plans. In this paper, we proposed a new scheme to classify

three types of brain tumors, namely, Meningioma, Glioma, and Pituitary tumors from MRI images. First, pre-processed is applied to images [70].

Recent laboratory advances in primary brain tumors have shown that specific molecular signatures can predict the biological behavior of tumors. Current brain tumor classification systems based on histology and morphology may soon be supplemented by a system based on molecular markers of tumor differentiation and progression [74].

## **12. Conclusion**

The quantitative, domain-specific data acquired through these studies will improve our understanding of brain toxicity and cognitive decline associated with radiation dosage to non-targeted tissue and can provide the basis for evidence-based cognition-sparing brain radiotherapy. Interestingly, this study introduces an association between certain WM diffusion changes and radiation-induced memory decline, which may indicate that there are other ROIs not studied in this paper that should be investigated as potentially vulnerable areas contributing to post-RT cognitive decline. Further research is needed to investigate the dynamic trajectories of tissue response to radiation to better understand how MRI changes can be used to predict important neurocognitive trajectories post-treatment [60].

Treatments and better outcomes for primary brain tumors have long lagged behind those of other tumors. However, a new era in neuro-oncology has emerged, with major advances in both cancer and CNS immunology, and progress in genomics [55].

### **Abbrevations**


*An Overview of Brain Tumor DOI: http://dx.doi.org/10.5772/intechopen.100806*
