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The tumor-draining lymph nodes (tdLN) are the initial site of metastases and are the prime site for generating robust antitumor responses. In this study, we explored the efficacy of a universal immune activator (ImmAct) targeted to the tdLN. This approach can be viewed as an attempt to turn a cold, unresponsive tdLN into a hot, responsive site. The adjuvant antitumor efficacy of our novel intranodal injection was evaluated in an aggressive metastatic mammary carcinoma murine model. The cancer cells were inoculated subcutaneously in the lower quadrant of the mouse to provoke the tdLN (inguinal lymph node). The study encompasses a range of methodologies, including in vivo and in vitro assays and high-dimensional flow cytometry analysis. Our findings demonstrated that intranodal administration of ImmAct following the dissection of the primary tumor led to improved tumor-free survival and minimized weight loss. ImmAct led to both local and systemic alterations in the cellular and humoral immunity. Additionally, after ImmAct treatment, non-responders showed a higher rate of exhausted CD8+ T cells compared to responders. Indeed, our innovative approach surpassed the gold standard surgery of sentinel lymph node excision. Overall, intranodal administration of ImmAct yielded a robust antitumor immune response, offering protection against micrometastases and relapse. [ABSTRACT FROM AUTHOR]

In patients with thyroid nodules, if the cervical lymph nodes gradually enlarge, a histological confirmation is required to rule out malignancy. Here is a case of benign intranodal thyroid tissue with cystic changes resembling lymph node metastasis of a papillary thyroid carcinoma. A 47-year-old man received ethanol sclerotherapy because of repeated enlargement of the thyroid gland 2 years prior to presentation. Subsequently, the patient underwent abscess removal from the deep neck and partial lobectomy of the attached left thyroid gland. Two months before the visit, extensive cervical lymphadenopathy was detected on ultrasonography (US) and computed tomography (CT). Total thyroidectomy and cervical lymph node dissection were performed to differentiate between metastatic papillary carcinoma of the thyroid gland and benign thyroid inclusions. Microscopic examination revealed multiple variable-sized nodules of benign thyroid follicles with cystic changes in both thyroid glands and bilateral cervical lymph nodes. An occult papillary microcarcinoma strongly positive for HBME-1 was also observed in the left thyroid lobe. However, the benign intranodal thyroid tissue was negative in both the real-time PCR-based BRAF V600E mutation test and HBME-1 immunohistochemical stain. Similarly, benign intranodal thyroid tissue can be enlarged by multiple cystic changes in a large number of lymph nodes along the neck node chain. For the differentiation of metastatic thyroid papillary carcinoma, real-time PCR-based BRAF V600E mutation test and HBME-1 immunohistochemical staining in addition to histological examination are helpful. [ABSTRACT FROM AUTHOR]

Simple Summary: In the field of cancer therapy, lymph nodes are important not only as targets for metastases resection but also as prudent target organs for cancer immunotherapy. Lymph nodes comprise a complete structure for the accumulation of a large number of T cells and their distribution throughout the body after antigen presentation and activation of dendritic cells. This review highlights current topics on the importance of lymph node structure in antitumor immunotherapy and intranodal-antigen-presenting mature dendritic cell vaccine therapy. We also discuss the rationale behind intranodal injection methods and their applications in neoantigen vaccine therapy, a new cancer immunotherapy. Hundreds of lymph nodes (LNs) are scattered throughout the body. Although each LN is small, it represents a complete immune organ that contains almost all types of immunocompetent and stromal cells functioning as scaffolds. In this review, we highlight the importance of LNs in cancer immunotherapy. First, we review recent reports on structural and functional properties of LNs as sites for antitumor immunity and discuss their therapeutic utility in tumor immunotherapy. Second, we discuss the rationale and background of ultrasound (US)-guided intranodal injection methods. In addition, we review intranodal administration therapy of tumor-specific-antigen-pulsed matured dendritic cells (DCs), including neoantigen-pulsed vaccines. [ABSTRACT FROM AUTHOR]