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Recent breakthroughs in cancer immunotherapy have led to curative efficacy and significantly prolonged survival in a subset of patients of multiple cancer types; and immunotherapy has become the newest pillar of cancer treatment in addition to surgery, chemotherapy, radiotherapy and precision targeted therapies. In the metastatic disease setting, responses to immunotherapy are heterogeneous depending on the metastatic organ sites. The tissue-specific immuno-biology in the tumor microenvironments (TMEs) contributes to the differential therapeutic responses. Herein, we review the impact of tissue-specific tumor microenvironment on the efficacy of immunotherapy, with a focus on historically under-represented central nervous system (CNS) metastasis, which was excluded from most clinical trials. Retrospective examination of patient specimens and prospective clinical studies with immune checkpoint blockade (ICB) have established that brain can harbor an "active" immune microenvironment for effective immunotherapy. Regulation by the innate immune microglial cells and remodeling of the blood–brain barrier (BBB) may contribute to immunotherapeutic responses mediated by T lymphocytes. How to convert an "inactive" (cold) brain microenvironment into an "active" (hot) brain TME should be the focus of future efforts. Thus, procurement and complete examination of clinical specimens from brain metastases as well as development of appropriate preclinical brain metastasis models susceptible to external manipulation of the TME are critical steps towards that goal. A deeper understanding of the immuno-biology in distinct organ microenvironments will help to expand the benefits of immunotherapy to more needed patients. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC. [ABSTRACT FROM AUTHOR]

Background: The tumor microenvironment contributes to tumor initiation, growth, invasion, and metastasis. The tumor microenvironment is heterogeneous in cellular and acellular components, particularly structural features and their gene expression at the inter-and intra-tumor levels. Main text: Single-cell RNA sequencing profiles single-cell transcriptomes to reveal cell proportions and trajectories while spatial information is lacking. Spatially resolved transcriptomics redeems this lack with limited coverage or depth of transcripts. Hence, the integration of single-cell RNA sequencing and spatial data makes the best use of their strengths, having insights into exploring diverse tissue architectures and interactions in a complicated network. We review applications of integrating the two methods, especially in cellular components in the tumor microenvironment, showing each role in cancer initiation and progression, which provides clinical relevance in prognosis, optimal treatment, and potential therapeutic targets. Conclusion: The integration of two approaches may break the bottlenecks in the spatial resolution of neighboring cell subpopulations in cancer, and help to describe the signaling circuitry about the intercommunication and its exact mechanisms in producing different types and malignant stages of tumors. [ABSTRACT FROM AUTHOR]