Discovering dominant tumor immune archetypes in a pan-cancer census.

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here "archetypes"-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy.

Identification of two theranostic biomarker panels for epithelial ovarian cancer.

BACKGROUND: Epithelial Ovarian cancer (EOC) is the leading cause of death associated with gynecologic tumors. Because the disease is asymptomatic in early-stage, the majority of patients are not diagnosed until late stages, highlighting the need for the development of novel diagnostic biomarkers. Mediators of tumoral microenvironment may affect EOC progression and resistance to treatment. AIM OF THE STUDY: Analysis of serum proteins to identify a panel of theranostic biomarkers for EOC. PATIENTS AND METHODS: Serum levels of 65 analytes were determined in EOC patients, and healthy controls with the ProcartaPlex Human Immune Monitoring 65-Plex Panel. RESULTS: Twenty-one analytes: 7 cytokines (IFN-γ, IL-12p70, IL-13, IL-18 and TSLP), 7 chemokines (Eotaxin, eotaxin-2, IP-10, BLC, I-TAC, SDF-1α, and fractalkine), 2 growth factors (MMP-1, VEGF-α), and 5 soluble receptors (APRIL, CD40L, TWEAK, CD30 and TNFRII; were significantly differentially expressed between the two groups. ROC curves showed that only seven of them (IL-9, TNF-α, Eotaxin, IP-10, BLC, Fractalkine, and Tweak) had AUC values greater than 0.70 and thus had potential clinical utility. Moreover, five cytokines: IFN-γ, IL-1 ß, IL-8, MIP-1ß, and TNF-α are positively associated with patients who developed resistance to taxol-platinum-based chemotherapy (CT). CONCLUSION: This study has revealed a first panel of 7 analytes (IL-9, TNF-α, Eotaxin, IP-10, BLC, Fractalkine and Tweak) that can be used for early detection of EOC and a second panel of five cytokines (IFN-γ, IL-1ß, IL-8, MIP-1ß, TNF-α) that can help clinicians to identify EOC patients who are at higher risk to develop resistance to CT of EOC.

Exploring the Potential of Plant-Based Nanotechnology in Cancer Immunotherapy: Benefits, Limitations, and Future Perspectives.

Reconceptualizing cancer immunotherapy can be improved if combined with plant production systems and nanotechnology. This review aims to contribute to the knowledge of plant use in nanomedicine and cancer immunotherapy. In the foreground, we outlined each of these approaches; nanomedicine, green synthesis, and immunotherapy. The benefits of plant-based nanoparticles in mending the immune systems were subsequently analyzed, with reference to the literature. The combining effects of biological and therapeutic properties of some phytochemicals and their derivatives, with targeted nanoparticles and selective immunotherapy, can enhance the delivery of drugs and antibodies, and induce antitumor immune responses, via activation of functions of neutrophils, lymphocyte cells, and natural killer cells, and macrophages, resulting in induced apoptosis and phagocytosis of tumor cells, which can improve designing immunotherapeutic strategies targeting cancer, with a larger spectrum compared to the current cytotoxic anticancer drugs commonly used in clinics. This study uncovers the mechanistic drivers of cancer immunoengineering in cancer therapy using plant-based nanomaterials, enhancing therapeutic benefits while minimizing toxic and side effects.

Roles of extracellular vesicles in glioblastoma: foes, friends and informers.

Glioblastoma (GB) tumors are one of the most insidious cancers which take over the brain and defy therapy. Over time and in response to treatment the tumor and the brain cells in the tumor microenvironment (TME) undergo many genetic/epigenetic driven changes in their phenotypes and this is reflected in the cellular contents within the extracellular vesicles (EVs) they produce. With the result that some EVs try to subdue the tumor (friends of the brain), while others participate in the glioblastoma takeover (foes of the brain) in a dynamic and ever changing process. Monitoring the contents of these EVs in biofluids can inform decisions based on GB status to guide therapeutic intervention. This review covers primarily recent research describing the different cell types in the brain, as well as the tumor cells, which participate in this EV deluge. This includes EVs produced by the tumor which manipulate the transcriptome of normal cells in their environment in support of tumor growth (foes), as well as responses of normal cells which try to restrict tumor growth and invasion, including traveling to cervical lymph nodes to present tumor neo-antigens to dendritic cells (DCs). In addition EVs released by tumors into biofluids can report on the status of living tumor cells via their cargo and thus serving as biomarkers. However, EVs released by tumor cells and their influence on normal cells in the tumor microenvironment is a major factor in immune suppression and coercion of normal brain cells to join the GB "band wagon". Efforts are being made to deploy EVs as therapeutic vehicles for drugs and small inhibitory RNAs. Increasing knowledge about EVs in the TME is being utilized to track tumor progression and response to therapy and even to weaponize EVs to fight the tumor.

9th Immunotherapy of Cancer conference (ITOC): A meeting report.

The Immunotherapy of Cancer conference (ITOC) is an European meeting providing a global platform for discussions where all those dedicated to the immunotherapy of cancer can exchange their knowledge and the latest findings about immuno-oncology. The 9th ITOC was held in Munich in September 2022. Major highlights of the 2022 edition included the key note address and life time achievement to Laurence Zitvogel on her contributions on the understanding of the role of microbiota in cancer development and therapy resistance. Her research has paved the way for therapeutic exploitation of the microbiome.

CAR T-cells for colorectal cancer immunotherapy: Ready to go?

Chimeric antigen receptor (CAR) T-cells represent a new genetically engineered cell-based immunotherapy tool against cancer. The use of CAR T-cells has revolutionized the therapeutic approach for hematological malignancies. Unfortunately, there is a long way to go before this treatment can be developed for solid tumors, including colorectal cancer. CAR T-cell therapy for colorectal cancer is still in its early stages, and clinical data are scarce. Major limitations of this therapy include high toxicity, relapses, and an impermeable tumor microenvironment for CAR T-cell therapy in colorectal cancer. In this review, we summarize current knowledge, highlight challenges, and discuss perspectives regarding CAR T-cell therapy in colorectal cancer.

The importance of microRNAs in the stroma-breast cancer cell interplay.

Breast cancer is one of the most diagnosed cancers in women. Despite outstanding progress over the past few years, breast cancer remains the second leading cause of cancer-related death among women. This fact emphasizes the need for improved diagnostic and prognostic markers, as well as improved understanding of cancer environment, including the crosstalk between epithelial and stromal cells. The tumor microenvironment is paramount in breast cancer progression and dissemination. Accumulating evidence indicates that epigenetic phenomena such as microRNAs are extremely important in cancer homeostasis. Through the improved understanding of the molecular mechanisms involved in the microenvironment-mediated promotion of cancer growth and metastasis, novel targets for therapeutic intervention or early diagnosis may be identified.