A Sampling of Highlights from the Literature: Article Recommendations from Our Deputy and Senior Editors.

Abstract

ILC3–T cell interactions regulate the gut microbiota (from Fig. 1C of Hakozaki et al., Cancer Immunol Res 2020)Group 3 innate lymphoid cells (ILC3) regulate host–microbe interactions in the intestines, but whether they have a role in colorectal cancer (CRC) is not known. Goc et al. show that ILC3s in human and mouse CRC are dysregulated. In mice, this reduces ILC3 interactions with CD4+ T cells, which decreases gut colonization by microbiota that induce type-1 immunity and thereby promotes CRC progression and resistance to PD-1 blockade. Patients with inflammatory bowel disease have dysregulated ILC3s and microbiota that do not induce type-1 immunity when transferred to mice, but rather promote CRC resistance to PD-1 blockade. The data identify new avenues for immunotherapeutic intervention.Goc J, …, Sonnenberg GF. Cell 2021 Aug 17. DOI: 10.1016/j.cell.2021.07.029.Autologous TIL ACT is effective and safe (by Shyamal via Wikimedia Commons)Adoptive cell therapy (ACT) for metastatic non–small cell lung cancer (NSCLC) has not yet been evaluated. Creelan et al. report on a phase I clinical trial testing ACT using autologous tumor-infiltrating lymphocytes (TIL) in patients with metastatic NSCLC that progressed despite nivolumab treatment. Autologous TIL ACT is effective and safe, and assessment after TIL treatment shows tumor-specific T cells are elevated in responding patients. The data highlight a potential new therapy option for patients with metastatic NSCLC.Creelan BC, …, Antonia SJ. Nat Med 2021 Aug 12;27:1410–8.HBV-specific CD8+ T cells infiltrate HCC (from GrahamColm at English Wikipedia via Wikimedia Commons)Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis B virus (HBV) infection, but whether HBV-specific T cells can control HCC growth is not known. Through comprehensive analysis of CD8+ T cells in samples from 46 patients with HCC, Cheng et al. show that HCC infiltration with HBV-specific CD8+ T cells associates with improved relapse-free survival. Intratumoral HBV-specific CD8+ T cells are enriched in two of five detectable subsets of tissue-resident memory T cells (Trm): CD103+CD57+ Trm and CD103+CD57− Trm. These cells are clonally expanded and lack gene signatures of terminally exhausted T cells, suggesting they could be harnessed therapeutically.Cheng Y, …, Newell EW. Immunity 2021 Aug 10;54:1825–40.e7.Overcoming treatment resistance in NSCLC can be achieved (from Librepath via Wikimedia Commons)Strategies to overcome resistance to anti–PD-1 immune checkpoint blockade in patients with cancer are much needed. By using genetically engineered models of non–small cell lung cancer (NSCLC), Martinez-Usatorre et al. identify mechanisms behind resistance to PD-1 blockade, antiangiogenic therapy, and the combination thereof. Tumor-associated macrophages of monocyte origin and alveolar origin contribute to resistance, and targeting these cells using a CSF1R inhibitor and cisplatin, respectively, improves responses to combination antiangiogenic therapy and PD-1 blockade. The data provide insight into the potential for targeting macrophages to overcome resistance to PD-1 blockade in patients with NSCLC.Martinez-Usatorre A, …, De Palma M. Sci Transl Med 2021 Aug 11;13:eabd1616.Improved CAR design improves performance (by Chris Phutully via Wikimedia Commons)Improving the antigen sensitivity of chimeric antigen receptor (CAR) T cells has the potential to improve responses in patients with tumors having low target antigen expression. Salter et al. compare T-cell receptor and CAR signaling in primary human T cells and show that multiple CD3 chains are not or are only weakly phosphorylated after CAR stimulation, indicating lower antigen sensitivity. Modifying the CAR construct to improve CD3 engagement increases CAR T-cell activation and efficacy in low antigen settings. The data highlight how understanding receptor signaling events can guide therapy design and provide potential construct alterations to improve CAR T-cell efficacy.Salter AI, …, Riddell SR. Sci Signal 2021 Aug 24;14:eabe2606.Immune profiling reveals inter- and intratumoral immune heterogeneity in PDAC (from Fig. 4C of Liudahl et al., Cancer Discov 2021)A deeper understanding of the pancreatic ductal adenocarcinoma (PDAC) tumor immune microenvironment is needed if effective immunotherapies are to be developed for this cancer. By analyzing 135 human PDAC samples using a single-cell multiplexed immunohistochemistry platform, Liudahl et al. provide insight into the inter- and intrapatient heterogeneity in density, complexity, phenotype, and spatial relationships of myeloid and lymphoid cells in PDAC. The data provide a comprehensive immune atlas of PDAC that can serve as a resource to stimulate further investigations.Liudahl SM, …, Coussens LM. Cancer Discov 2021 Aug 1;11:2014–31.