Adjuvant immunotherapy for non-small cell lung cancer

Changes in the local tumor microenvironment in recurrent cancers may explain the failure of vaccines after surgery

“…Cancer vaccines have been proposed to treat patients after surgery to prevent relapses by augmenting endogenous antitumor immune responses (5,6). This strategy has theoretical benefits such as low toxicity, tumor specificity, and long-lasting immunity.…”

“…This strategy has theoretical benefits such as low toxicity, tumor specificity, and long-lasting immunity. Most importantly, cancer vaccines are maximally effective for limited disease burden; thus postoperative administration is appealing because of the presence of minimal residual disease (4,6,7,8).…”

“…Accordingly, the treatment of minimal disease with cancer vaccines has been tested in hundreds of preclinical studies in animal models with small amounts of tumor burden (6,(9)(10)(11)(12)(13). These preclinical studies have translated to several trials of cancer vaccines to prevent recurrences in patients after surgery (6,12).…”

“…These preclinical studies have translated to several trials of cancer vaccines to prevent recurrences in patients after surgery (6,12). To date, responses have been infrequent despite the generation of antigen-specific effector T lymphocytes (5,6,14).…”

“…These preclinical studies have translated to several trials of cancer vaccines to prevent recurrences in patients after surgery (6,12). To date, responses have been infrequent despite the generation of antigen-specific effector T lymphocytes (5,6,14). One potential explanation for the discordance between preclinical studies and postoperative clinical trials is that most evidence was derived from xenograft or transgenic mouse models with primary tumors (12,15).…”