Milestones in Cancer Immunology | Free Article
Cancer Immunol Res November 1 2015 3 (11) 1193-1194; DOI:10.1158/2326-6066.CIR-15-0257
One treatment for metastatic melanoma is systemic IL2 with infusion of tumor-infiltrating lymphocytes (TILs). Intrathecal TIL administration, along with intrathecal IL2, briefly stabilized disease in this case, suggesting that such an approach might benefit a select patient population.
Type-I interferon immune signaling plays a critical role during the antimetastatic immune response. The authors show that loss of this pathway can promote bone metastasis in three different breast cancer models, revealing its importance across different models.
The presence of neutrophils in oral squamous cell carcinoma correlates with poor prognosis. The TNFα and IL8 secreted by neutrophils were found to increase the invasiveness of cancer cells through invadopodia formation and matrix degradation.
Colon cancers exhibit an increased IL22:IL10 ratio. The two cytokines share one receptor subunit, but their second receptor subunits are distinct. Colorectal cancer shows overexpression of both receptor subunits for IL22, which triggers STAT3 signaling and promotes carcinogenesis.
Myeloid-derived suppressor cells in tumors, but not in the spleen, activated fatty acid uptake and oxidation (FAO) and increased their immunosuppressive pathways. Blocking FAO with inhibitors induced T-cell–mediated antitumor activity, which provides a novel approach for treatment.
Carcinomas can overexpress brachyury, a transcription factor not expressed in most adult tissues. A therapeutic yeast vaccine targeting brachyury was tested in phase I clinical trials. It induced T-cell responses with no autoimmunity and showed preliminary clinical activity.
PARP inhibitors improve progression-free survival in BRCA1-deficient ovarian cancer. In a mouse model, checkpoint blockade with anti–CTLA-4, but not anti–PD-1, synergized with PARP inhibition to establish protective immune memory and achieve long-term survival.
Ovarian tumor ascites fluid contains an immunosuppressive element identified as phosphatidylserine from nanovesicle membranes, originating from the tumor milieu. Suppression was disrupted by addition of diacylglycerol kinase inhibitors, suggesting that blocking these vesicles may enhance patient antitumor activity.
An efficacious combination of immunomodulatory treatments was identified in a late-stage prostate cancer model that prevented tolerance, promoted a sustained tumor-specific CD8+ T cells response, and cured tumors when given with adoptively transferred tumor-specific T cells.