cDC1 emerge as a dominant response-associated feature within multicellular immune niches in melanoma and lung cancer — ASN Events
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  2. Poster Session 2
  3. cDC1 emerge as a dominant response-associated feature within multicellular immune niches in melanoma and lung cancer

cDC1 emerge as a dominant response-associated feature within multicellular immune niches in melanoma and lung cancer (#242)

Saraí G De León Rodríguez 1 2 , Jesús García-Gómez 3 , Cristina Aguilar-Flores 1 , Joahan K Martínez-Sarabia 1 , Ángel Juárez Flores 4 , Ezequiel M Fuentes-Pananá 4 , María Guadalupe Jazmín De Anda González 5 , Laura Bonifaz 6
  1. Unidad de Investigación Médica en Inmunología, UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico, Mexican Social Security Institute, Mexico City, Ciudad de México, México
  2. Programa de Doctorado en Ciencias Biológicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, Ciudad de México, México
  3. Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México
  4. Hospital infantil de México Federico Gómez, Mexico City, Ciudad de México, México
  5. Hospital de Oncología Centro Médico Nacional S.XXI. IMSS, Mexico City, Ciudad de México, México
  6. Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Ciudad de México, México

Type 1 conventional dendritic cells (cDC1) are critical mediators of antitumor immunity. We previously showed that cDC1 and TCF1+ and TCF1− tissue-resident memory (TRM) CD8 T cells are enriched in immune checkpoint blockade (ICB)-responsive melanoma and spatially associated within the tumor microenvironment. However, whether cDC1 represent dominant response-associated features within complex immune landscapes and participate in multicellular spatial architectures conserved across tumor types remains unclear. Here, we addressed this question through quantitative, predictive and spatial analyses in melanoma and NSCLC. Pretreatment melanoma biopsies from ICB-treated patients were analyzed by multiplex immunofluorescence and computational image analysis. Twelve quantitative immune variables were assessed. Redundant variables were removed by iterative variance inflation factor analysis, followed by LASSO and Elastic Net modeling. Spatial density analysis was performed in representative responders and non-responders, evaluating TCF1+ TRM, TCF1− TRM, cDC1, CD4 T cells, B cells, NK cells, macrophages, neutrophils, mast cells and tumor cells. Exploratory analyses were also performed in pembrolizumab-treated non-small cell lung cancer (NSCLC). cDC1 abundance showed the highest individual discriminatory performance for response (AUC=0.920; p=0.0001) and remained the most robust feature in both LASSO and Elastic Net models. When all 12 variables were analyzed, cDC1 again ranked first. PCA using the top four selected variables showed clearer responder/non-responder separation than the complete 12-variable profile. Spatial profiling revealed recurrent high-density regions containing cDC1, TCF1+ and TCF1− TRM, and B cells in responding melanomas, whereas this organization was reduced or lost in non-responders. Preliminary NSCLC analyses similarly showed increased cDC1 in pembrolizumab responders and a comparable spatial pattern. Together, these findings identify cDC1 as a dominant feature of ICB-responsive tumor microenvironments and extend previous TRM–cDC1 observations toward broader multicellular immune niches. Preliminary cross-tumor findings suggest that cDC1-associated spatial organization may represent a conserved feature of effective antitumor immunity.