Tumor suppressor maspin as a modulator of host immune response to cancer

Abstract

Despite the promising clinical outcome, the primary challenge of the curative cancer immunotherapy is to overcome the dichotomy of the immune response: tumor-evoked immunostimulatory versus tumor-induced immunosuppressive. The goal needs to be two-fold, to re-establish sustainable antitumor-cancer immunity and to eliminate immunosuppression. The successful elimination of cancer cells by immunosurveillance requires the antigenic presentation of the tumor cells or tumor-associated antigens and the expression of immunostimulatory cytokines and chemokines by cancer and immune cells. Tumors are heterogeneous and as such, some of the tumor cells are thought to have stem cell characteristics that enable them to suppress or desensitize the host immunity due to acquired epigenetic changes. A central mechanism underlying tumor epigenetic instability is the increased histone deacetylase (HDAC)-mediated repression of HDAC-target genes regulating homeostasis and differentiation. It was noted that pharmacological HDAC inhibitors are not effective in eliminating tumor cells partly because they may induce immunosuppression. We have shown that epithelial-specific tumor suppressor maspin, an ovalbumin-like non-inhibitory serine protease inhibitor, reprograms tumor cells toward better differentiated phenotypes by inhibiting HDAC1. Recently, we uncovered a novel function of maspin in directing host immunity towards tumor elimination. In this review, we discuss the maspin and maspin/HDAC1 interplay in tumor biology and immunology. We propose that maspin based therapies may eradicate cancer.

Maspin as a Prognostic Marker for Early Stage Colorectal Cancer With Microsatellite Instability

“…Future work is needed to elucidate the functional role of the enzyme maspin in MSI cancers and the mechanistic basis for maspin-associated differential clinical behavior. It is possible that maspin enhances immune recognition of MSI cancers (28,29), and maspin might play a synergistic role during checkpoint inhibitor therapy. Our recent discovery that maspin is part of the CRC autoantigen-ome that elicits a cancer-directed humoral immune response is a promising step in this direction (7).…”

Do Hematological Parameters Have a Significant Role in Predicting the Results of Prostate Biopsies?

“…As mentioned above, there are many inconsistent results regarding the predictive value of NLR in the detection and prognosis of prostate cancer. Over the past two decades, we have come to understand that the cells of immune system in cancer perform two different actions as antitumoral and immunosuppressive activities, thereby leading to tumor progression (12) . Neutrophils and lymphocytes contain different subgroups.…”

“…Neutrophils and lymphocytes contain different subgroups. Neutrophils contain cells with an antitumor phenotype (N1) and a pro-tumor phenotype (N2), and some T lymphocytes have both pro-and antitumoral properties (10)(11)(12) . When we calculated the NLR, we considered all neutrophil and lymphocyte cells without discriminating between the subgroups.…”

Desmocollin 3 Gene (Dsc3) Expression and Cancer - In Silico Evaluation

“…ΔNP63 is also known oncogene which promotes cancer development but controls invasion and metastasis (Srivastava et al,2018). DSC3, PKP1, Maspin and PERP (Green et al,2019) are known for tumour suppression and inhibition of tumour invasion and metastasis (Jodi et al,2014, Dzinic et al, 2015, Bodenstine et al,2012, Lockett et al,2005. All these factors might have contributed to correlation between DSC3 expression and better survival.…”