Scientists have identified how an RNA named EPIC1 endows tumors with the ability to resist immunotherapies – and show that targeting the RNA in cells and mice can potentiate checkpoint blockade and slow tumor growth. Despite their clinical success, immunotherapies such as PD-1 blockade still face many obstacles that impede their effectiveness. Many patients aren’t eligible for immunotherapy, and those who are eligible don’t always respond to treatment. Furthermore, tumors often adapt over time to resist these treatments, leading to high relapse rates and poor outcomes. Scientists are now searching for proteins and other molecules that enable tumors to resist treatments, theorizing that targeting such factors could boost the cancer-killing power of immunotherapy. In this study, Dhamotharan Pattarayan and colleagues identified one such target in EPIC1, a long noncoding RNA that contributes to tumor evasion. They examined human breast cancer cells and found that EPIC1 restrained immunity against tumor cells by suppressing type I interferon signaling and the accumulation of double-stranded RNAs, which normally facilitate antitumor responses, in the tumor cells. EPIC1 orchestrated these effects by inhibiting the activation of various types of retroelements, which are DNA sequences that can move around within genomes and produce double-stranded RNAs when activated. Reducing EPIC1 levels restored double-stranded RNA production in cancer cells and revived antitumor immune responses. Pattarayan et al. also showed that oligonucleotides that target EPIC1 for degradation slowed the growth of triple-negative breast cancer tumors in mice and boosted the infiltration of T cells and macrophages into tumors. Knocking down EPIC1 also sensitized tumor-bearing mice to treatment with the approved PD-1 inhibitor pembrolizumab, highlighting EPIC1’s viability as a potential therapeutic target. For reporters interested in trends, an August study in Science Immunology revealed how inhibiting the cell cycle protein BUB1 sensitizes tumors to radiation therapy and immunotherapy by activating innate immunity: www.science.org/doi/10.1126/sciimmunol.adq2055

Algorithms submitted for an AI Challenge hosted by the Radiological Society of North America (RSNA) have shown excellent performance for detecting breast cancers on mammography images, increasing screening sensitivity while maintaining low recall rates, according to a new study.

Breastfeeding reduces breast cancer risk by 22%–50% for BRCA gene mutation carriers, study shows. Despite the protective role of breastfeeding, early detection remains important for high-risk groups such as women with family histories of breast cancer.

Meriem Bahri and colleagues have developed an orally available, small-molecule inhibitor that targets heme oxygenase 1 enzyme (HO-1) in a subset of tumor-associated macrophages that reside near the vasculature. The inhibitor treatment along with chemotherapy reduced tumor growth in mouse models of breast cancer and sarcoma. The findings suggest a way to target this population of immunosuppressive cells therapeutically, the researchers conclude. The inhibitor drug targets perivascular tumor-associated macrophages (PvTAMs) that express the LYVE-1 receptor. These cells rely on heme oxygenase to maintain an immunologically “cold” tumor — one that doesn’t trigger a strong immune response and has few tumor-infiltrating CD8+ T cells. Non-specific targeting of tumor-associated macrophages has not been an effective antitumor strategy, so Bahri et al. looked for a way to target this specific cell population instead. The KCL-HO-1i inhibitor developed by the team improved the effects of the chemotherapeutic agents gemcitabine or 5-fluorouracil to reduce tumor growth in mice, and the combination allowed more CD8+ T cells to infiltrate the tumors compared with chemotherapy alone.