Immune microenvironments in solid tumors: new targets for therapy

SL Shiao, AP Ganesan, HS Rugo… - Genes & …, 2011 - genesdev.cshlp.org
SL Shiao, AP Ganesan, HS Rugo, LM Coussens
Genes & development, 2011genesdev.cshlp.org
Leukocytes and their soluble mediators play important regulatory roles in all aspects of solid
tumor development. While immunotherapeutic strategies have conceptually held clinical
promise, with the exception of a small percentage of patients, they have failed to
demonstrate effective, consistent, and durable anti-cancer responses. Several subtypes of
leukocytes that commonly infiltrate solid tumors harbor immunosuppressive activity and
undoubtedly restrict the effectiveness of these strategies. Several of these same immune …
Leukocytes and their soluble mediators play important regulatory roles in all aspects of solid tumor development. While immunotherapeutic strategies have conceptually held clinical promise, with the exception of a small percentage of patients, they have failed to demonstrate effective, consistent, and durable anti-cancer responses. Several subtypes of leukocytes that commonly infiltrate solid tumors harbor immunosuppressive activity and undoubtedly restrict the effectiveness of these strategies. Several of these same immune cells also foster tumor development by expression of potent protumor mediators. Given recent evidence revealing that immune-based mechanisms regulate the response to conventional cytotoxic therapy, it seems reasonable to speculate that tumor progression could be effectively diminished by combining cytotoxic strategies with therapies that blunt protumor immune-based effectors and/or neutralize those that instead impede development of desired anti-tumor immunity, thus providing synergistic effects between traditional cytotoxic and immune-modulatory approaches.
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