JAML (Junction Adhesion Molecule Like)

It was also linked to reduced cisplatin/paclitaxel sensitivity (P < 0.05) and lower immunotherapy response (29.04% vs. 45.05%, P = 0.015). These findings suggest that JAML deficiency may suppress cyclic GMP-AMP synthase (cGAS)-STING pathway activation, potentially contributing to M1/M2 macrophage polarization imbalance and facilitating EC progression. Clinically, JAML expression shows promise as a potential biomarker for prognostic stratification and treatment response prediction (chemotherapy/immunotherapy), providing insights for developing precision immunochemotherapy strategies in EC.

CRC cells with JAML overexpression are more sensitive to radiotherapy of X-rays because of the decreased phosphorylation of the ATR-CHK1-mediated DNA damage repair pathway. The expression of JAML in CRC cells could be used as a predictive biomarker of radiosensitivity in patients with CRC.

Particular attention is given to the effects of JAML on tumor cell proliferation and migration, alongside its pivotal role in regulating lymphocyte infiltration into the tumor microenvironment. Collectively, The balance between JAML's pro-inflammatory and anti-tumor functions underscores its therapeutic promise.

Pathway enrichment analysis further revealed that JAML enhances CTL responses through the oxidative phosphorylation pathway. Activation of JAML enhances CTL responses in HCC treatment, independent of αPD-L1-mediated immunotherapy, providing a promising strategy for advanced HCC.

This study concluded that JAML is specifically highly expressed in the vascular endothelial cells of tumour, promoting tumour progression by angiogenesis through the activation of the FAK/SRC/ERK/AKT pathway and VEGF/VEGFR2 pathway. JAML might be a new target for antiangiogenesis and provide valuable insights into the development of novel therapeutic approaches for cancer patients.

TILs were reduced in JAML-high tumour tissues by decreasing chemokines such as CCL20 and CXCL9/10/11. Our study identified JAML, a potentially ideal target that is specifically highly expressed in CRC tissues, which promoted tumour proliferation, impaired T-lymphocytes infiltration, provided a promising therapeutic strategy for patients with CRC.

Our study reveals an intrinsic bias of CD8+TRMs for receiving the tumor-derived costimulatory signal in the TME, which sustains their innate-like function and antitumor role. These findings will shed more light on the biology of CD8+TRMs and aid in the development of potential targeted treatment strategies for NSCLC.

JAML is a novel target for kaempferol against LUAD cells. Please cite this article as: Wu Q, Wang YB, Che XW, Wang H, Wang W. Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma. J Integr Med. 2023; 21(3): 268-276.

When compared with other immunotherapy targets plagued by low target specificity and end-organ toxicity, we find JAML to be mostly restricted to and highly expressed by tissue-resident memory CD8 T cells in multiple cancer types. By delineating the key cellular targets and functional consequences of agonistic anti-JAML therapy in a murine melanoma model, we show its specific mode of action and the reason for its synergistic effects with anti-PD-1.

Our data reveal the oncogenic role of JAML in LUAD, indicating that JAML may be a predictive biomarker and novel therapeutic target for LUAD.

CONCLUSIONS JAML expression was significantly correlated with prognosis and immune infiltrates. These preliminary findings suggested JAML could be considered as a potential prognostic biomarker and therapeutic target for LUAD.

Our study suggested that AMICA1 might function as a diagnostic and prognostic biomarker and significantly suppressed the proliferation of LUAD cells. Besides, AMICA1 is positively correlated with immune cells infiltration in LUAD, and cGAS-STING signaling might play an important role in the process.