RESUMO
Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) antibodies, have initiated a new era in the treatment of malignant melanoma. ICIs can be used in various settings, including first-line, adjuvant, and neo-adjuvant therapy. In the scope of this review, we examined clinical studies utilizing ICIs in the context of treating oral mucosal melanoma, a rare disease, albeit with an extremely poor prognosis, with a specific focus on unraveling the intricate web of resistance mechanisms. The absence of a comprehensive review focusing on ICIs in oral mucosal melanoma is notable. Therefore, this review seeks to address this deficiency by offering a novel and thorough analysis of the current status, potential resistance mechanisms, and future prospects of applying ICIs specifically to oral malignant melanoma. Clarifying and thoroughly understanding these mechanisms will facilitate the advancement of effective therapeutic approaches and enhance the prospects for patients suffering from oral mucosal melanoma.
Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Terapia Combinada , Imunoterapia , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
BACKGROUND: Salivary duct carcinoma (SDC) is a rare, extremely aggressive malignancy that arises in the submandibular gland. It can metastasize locally early and therefore is an important differential diagnosis of metastatic disease in cervical lymph nodes or specific lymphadenitis such as tuberculous cervical lymphadenitis. CASE SUMMARY: We report a case of SDC in the submandibular gland that presented diagnostic difficulty. The lesion was coincidentally discovered through examination of the radiolucent area of the maxilla. Imaging failed to confirm the possibility of specific inflammation, leading us to execute an open biopsy to verify the diagnosis. The surgical specimen showed that the submandibular gland was primarily replaced with a calcified body. Following histological analysis and confirmation, we performed surgical resection, radiotherapy, and various chemotherapies. CONCLUSION: Radiographic imaging characteristics of lymph node metastases of salivary gland cancer, especially of SDC, may resemble other cervical lymphadenitis; calcification at the submandibular gland is the landmark of SDC occurring at the subman-dibular gland.
RESUMO
Melanoma is an aggressive type of cancer originating from the skin that arises from neoplastic changes in melanocytes. Transforming growth factorß (TGFß) is a pleiotropic cytokine and is known to contribute to melanoma progression by inducing the epithelialmesenchymal transition (EMT) program and creating an environment that favors tumor progression. There are three TGFß isoforms, TGFß1, TGFß2 and TGFß3, all of which engage in protumorigenic activities by activating SMAD signaling pathways. All TGFß isoforms activate signaling pathways by binding to their TGFß type I (TßRI) and type II (TßRII) receptors. Thus, effective targeting of all TGFß isoforms is of great importance. In the present study, chimeric proteins comprising the extracellular domains of TßRI and/or TßRII fused with the Fc portion of human immunoglobulin (IgG) were validated in the melanoma context. The Fc chimeric receptor comprising both TßRI and TßRII (TßRITßRIIFc) effectively trapped all TGFß isoforms. Conversely, TßRIIFc chimeric receptor, that comprises TßRII only, was able to interact with TGFß1 and TGFß3 isoforms, but not with TGFß2, which is a poor prognostic factor for melanoma patients. Accordingly, it was revealed that TßRITßRIIFc chimeric receptor suppressed the EMT program in melanoma cells in vitro induced by any of the three TGFß isoforms, as revealed by decreased expression of mesenchymal markers. Conversely, TßRIIFc chimeric receptor inhibited the EMT program induced by TGFß1 and TGFß3. In addition, it was established that tumor growth in subcutaneous mouse melanoma was inhibited by TßRITßRIIFc chimeric receptor indicating that Fc chimeric receptor could be applied to modify the tumor microenvironment (TME) of melanoma. Therefore, designing of Fc chimeric receptors targeting TGFß signals that affect various components of the TME may result in the development of effective antimelanoma agents.