Table 1.

Summary of Immunomodulatory Effects of Platinum Drugs.

Immunomodulation:	Effect of Modulation:	GBM Significance:	Refs:
Reduce PD-L Expression	Decreases inhibitory signals that hamper anti-tumor immune responses	GBM cells upregulate expression of PD-L, hindering anti-tumor T cell responses	17,19,31
Increase MHC I Expression	Improves tumor cell recognition by the immune system	GBM cells reduce MHC class I expression, leading to impaired antigen presentation	17,19,32,33
Inhibit STAT Signaling	Inhibits pathways involved in numerous oncogenic processes, including immunosuppression	Aberrant STAT signaling is found in many GBM tumors and contributes to immunosuppression	25-27, 32-34
Alter Tumor Microenvironment Immune Cell Profile	Reduces immunosuppressive cells including, Tregs and MDSCs, and increases CTLs	GBM induces numerous immunosuppressive cell types which enhance immunosuppression	17, 19, 32, 34-36
Increase M6P Expression	Enhances CTL anti-tumor activity by altering cancer cell sensitivity to the pro-apoptotic serine protease, granzyme-B	GBM cells suppress anti-tumor CTL responses	17,19, 37
Immunogenic Cell Death	Generates ‘immunological memory’ enabling durable anti-tumor immune responses	GBM cells effectively evade and suppress the immune system, preventing durable anti-tumor immune responses	17,19, 33

Abbreviations: CTL, cytotoxic T lymphocyte; GBM, glioblastoma; M6P, mannose 6-Phosphate; MDSC, myeloid derived suppressor cells; MHC, major histocompatibility complex; PD-L, programmed death ligand; STAT, signal transducers and activators of transcription; Treg, regulatory T-cell