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eliminates foreign pathogens, minimizing the duration of an inflammatory, tumor-promoting environment.
It is also understood that the immune system can impact the immunogenicity of the tumor itself given intact
immune systems impact the very nature of the tumor and contribute to its ability to progress and grow.
Understanding the impact of the immune system, including this knowledge of “cancer immunoediting” has
[1]
allowed for the development of additional therapies to treat cancer . Various classes of immunotherapies
now exist that attempt to harness and exploit different strengths of the immune system, ranging from
[2]
adoptive T cell therapy and cytokine therapy to checkpoint blockade therapy and oncolytic virus therapy .
Our improved understanding of the central nervous system (CNS) over the last several decades has led to the
growth and continuous innovative design of immunotherapeutics for different malignancies, including those
in the CNS. Lymphatics have been identified in the meninges and the dura, demonstrating a communication
[3]
route for lymphocytes to and from the brain and cervical lymph nodes . We also now know that the CNS
has processes of immunosurveillance which allow for autoimmune disease and paraneoplastic syndromes
to exist within its realm. The immune sytem can thus be used to our advantage in fighting cancer even in
the CNS, contrary to prior belief. It has been shown that T cells infused intravenously will make their way
to the central nervous system, but there are still many challenges to resolve before we are able to harness
[4]
the immune system to attack cancer without excessive toxicity . The responses to antigens must be narrow
and limited only to those particular epitopes; otherwise, the response can spread and damage healthy,
normal brain tissue. Tumor specific mutations are also less common in brain tumors compared to other
malignancies, and may be unique to each individual, requiring optimal individualized medicine which can
[5]
be cost-prohibitive . Another challenge is that gliomas appear to have natural mechanisms to inhibit T cell
activation and actually decrease peripheral T-cell counts, resulting in the lymphopenia seen in these patients
[6]
even prior to the initiation of therapy . Glioma cells are even able to evade detection by the immune
system by down-regulating major histocompatibility complexes (MHC) or other components necessary for
[7]
antigen presentation . Thus, there are many avenues and opportunities for further exploration in the field
of immunotherapy as it relates to brain tumor treatments, and as we learn and understand more, we slowly
improve in our ability to develop novel therapeutics for CNS tumors.

ADOPTIVE CELL THERAPIES - INTRODUCTION TO CHIMERIC ANTIGEN RECEPTOR-T
The ability to harness the body’s own immune system to create a sustained anti-tumor response has
transformed conventional therapeutic strategies for patients with cancer. Cell-based therapies involve the
allogeneic or autologous transfer of immune-derived cells into cancer patients to enhance the host immune
[8,9]
system’s ability to recognize and destroy cancer cells . T-lymphocytes are the backbone of the body’s
defense system due to their critical role in orchestrating and executing an effective immune response. They
have been identified as prime candidates for their robust response against foreign pathogens and persistent
[10]
anti-tumor activity . Although endogenous T cells are frequently unable to eradicate progressing tumor
on their own, modern technology has made it possible to genetically engineer the function, specificity, and
longevity of T-cell anti-tumor response. Perhaps most importantly, the adoptive transfer of these cells can
elicit a high degree of efficacy and specificity, thus, minimizing off-target toxicities.

Adoptive T-cell therapy (ACT) consists of isolating, expanding and reintroducing tumor-specific T lym-
phocytes into patients with cancer. Currently, there are four forms of ACT actively being investigated for
cancer treatment: (1) tumor-infiltrating lymphocytes (TILs); (2) cytotoxic T lymphocytes (CTLs); (3) T-cell
receptors (TCRs); and (4) chimeric antigen receptors (CARs) [Table 1] [9,11] . TILs have unique anti-tumor
properties as they are extracted from tumor biopsies where they have been exposed and conditioned to the
tumor microenvironment. These cells can be isolated from tumor tissue and expanded in IL-2 cytokine
prior to re-introduction and have shown to be an effective approach for patients with metastatic malignant
[12]
melanoma . CTLs are naturally circulating tumor-specific T cells taken from a patient’s peripheral blood
and can be expanded using antigen presenting cells (APCs). Both TILs and CTLs, once infused back into the
patient, recognize tumor associated antigens (TAA) via their TCR as antigeneic peptides presented by MHC,