**4. Discussion**

The ability of the GK-1 peptide to increase survival, significantly to delay tumor growth, and to reduce metastasis is discussed in this review. Considering that the immune system plays a crucial role in the outcome of cancer, orchestrating the response that may lead either to the control or dissemination of tumors [8, 78, 104], understanding the mechanisms that underlie the efficient response to the peptide is imperative.

**Acknowledgements**

**Conflict of interest**

**Abbreviations**

Universidad Nacional Autónoma de México.

APC antigen-presenting cell CCL-22 chemokine ligand-22 CTL cytotoxic T lymphocytes

HDP host defense peptides

NK natural killer cells

Treg regulatory T cell

PD-1 programmed cell death 1 PD-L1 programmed death-ligand 1

TM tumor microenvironment

VEGF vascular endothelial growth factor

DC dendritic cell

CTLA-4 cytotoxic T-lymphocyte antigen 4

LAG-3 lymphocyte-activation gene 3

MDSC myeloid-derived suppressor cells

PAMPs pathogen-associated molecular patterns

STAT3 signal transducer and activator of transcription 3

VEGFR-2 vascular endothelial growth factor receptor 2

This work was supported by CONACyT (253891), Fundación Miguel Alemán, and the Programa de Investigación para el Desarrollo y la Optimización de Vacunas, Inmunomoduladores y

Understanding the Anti-Tumor Properties Mediated by the Synthetic Peptide GK-1

http://dx.doi.org/10.5772/intechopen.79833

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The authors acknowledge the financial assistance of CONACyT to the doctoral students Jacquelynne Cervantes-Torres, Laura Montero-León, and Diana Torres-García from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), who received the fellowships 25243, 29951, and 245638, respectively. This manuscript is part of the doctoral thesis of the students from the Instituto de Investigaciones Biomédicas at the

Métodos Diagnósticos del Instituto de Investigaciones Biomédicas, UNAM.

The authors declare no financial or commercial conflict of interest.

It has been reported that the production of pro-inflammatory cytokines both by tumor and surrounding cells, along with the production of growth factors and chemokines, can promote the development of neoplasia by facilitating carcinogenesis programs, inducing a sustained cellular proliferative rate, inhibiting apoptosis and stimulating angiogenesis [105, 106]. As described above, GK-1 therapy contributed to decrease the levels of IL-4, IL-10, b-FGF, and GM-CSF; these chemoattractants, along with hypoxia, promote macrophage shift from a M1 to a M2 phenotype. M2-like tumor-associated macrophages (TAM) stimulate immunosuppression and increase blood vessel density, favoring angiogenesis. In a breast cancer model, lower CCL2 and CCL3 levels in the lungs of mice treated with GK-1 could be decreasing the migration of inflammatory monocytes such as MAM and MDSC, which promote metastasis [8, 13, 102, 107]. These changes in the microenvironment seem to contribute to control tumor burden and metastasis.

On the other hand, M1-like macrophages can contribute to tumor regression by recruiting cytotoxic CD8+ T (CTL) and NK cells [108–110]. In this regard, IL-12 induction by APCs could be contributing to the increase in the proliferation of CD8+ and CD4+ lymphocytes and the induction of a Th1 response, as previously reported [51, 52, 111]. Several studies have suggested a correlation of higher density levels of cytotoxic (CTL) and memory T lymphocytes (CD3+ CD45RO+) infiltrated in the primary tumor with increased survival rates of patients with different types of neoplasms [91, 112–116].

According to recent findings, the GK-1 peptide can induce a M1 phenotype and promote the efficient activation of DCs, which could be leading to the maintenance of an effector response against tumor growth, capable of counteracting the immunosuppressive response due to T cell exhaustion or DC dysfunction.
