Targeting Immune-Related Molecules in Cancer Therapy: A Comprehensive In Vitro Analysis on Patient-Derived Tumor...

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Colorectal cancer (CRC) exhibits diverse molecular subtypes.
• Immunosuppressive checkpoint molecules are prevalent in CRC, with variable indolamine 2,3-dioxygenase (IDO) expression.
• Immune-related molecule presence is independent of CRC molecular subtype.

Purpose of the Study:

• To investigate the impact of immune-related pathway inhibition, including IDO, on CRC cell growth and viability.
• To evaluate the efficacy of Indoximod, Curcumin, and Gemcitabine, alone and in combination with peripheral blood lymphocytes (PBL).
• To assess the potential of combined therapies in stimulating antitumor immune responses.

Main Methods:

• Phenotyping of 17 patient-derived CRC cell lines.
• Selective treatment of CRC cell lines with high or low IDO expression using single agents and combinations.
• Inclusion of allogeneic peripheral blood lymphocytes (PBL) in treatment regimens.
• Analysis of CRC cell growth, viability, apoptosis, necrosis, and cellular senescence.

Main Results:

• All tested agents affected CRC cell growth in a cell line-specific manner.
• The combination of Curcumin and Gemcitabine demonstrated the highest efficacy in tumor cell elimination.
• Curcumin alone induced significant apoptosis; necrosis was not detected.
• Addition of PBL generally enhanced the antitumoral effects of IDO inhibitors, achieving up to 80% cytotoxicity with Curcumin treatment.

Conclusions:

• Combined Curcumin and low-dose chemotherapy represent a promising strategy for eliminating colorectal cancer cells.
• This combined approach effectively stimulates antitumor immune responses.
• Targeting IDO pathways and combining with chemotherapy and immunotherapy holds potential for CRC treatment.