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Background: IMMUcan (SPECTA NCT02834884) is a European public-private effort to generate molecular and cellular profiling data of the human tumor microenvironment (TME) from up to 3,000 patients, to better understand how the immune system and tumors interact. Triple-negative breast cancer (TNBC) is a heterogenous disease with distinct molecular subtypes characterized by different gene expression, genomic profiles, and clinical outcomes. Here, we explored the association between molecular subtypes and response to neoadjuvant chemotherapy as well as levels of immune cell infiltration in the prospective IMMUcan TNBC cohort. Methods: At the cut-off date on June 29th, 2022, we identified a first cohort of 132 patients to perform preliminary analyses, of which 109 had pre-treatment RNAseq data available. Among those, pathological Complete Response (pCR) information was available for a total of 86 patients. Preliminary data included the density of CD3+, CD20+ and CD8+ immune cells from the stroma and tumor compartments from multiplex-immunofluorescence (mIF) for 69 patients. TNBC subtypes were computed as described by Bareche et al. Association of continuous variables with pCR was evaluated with logistic regression (univariate analysis). Results: The pCR rates differed across TNBC subtypes (Fisher’s test, P = 0.02). In detail, pCR was achieved in 88% (8/9) of basal like (BL), 63% (17/27) of immunomodulatory (IM) and 45% (16/35) of mesenchymal (M) tumors, while lower pCR rates were observed for the mesenchymal stem-like (MSL) and luminal androgen receptor (LAR) subtypes with 37% (3/8) and 14% (1/7), respectively, suggesting differences in the sensitivity to neoadjuvant chemotherapy in line with previous reports. When considered as continuous signature scores, pCR was positively associated to BL levels (OR = 2.7, 95% CI, 1.5-4.8; False Discovery Rate [FDR] = 0.0031), and negatively associated to MSL and LAR signature levels (OR = 0.53, 95% CI, 0.32-0.87; FDR = 0.019; OR = 0.30, 95% CI, 0.12-0.74; FDR= 0.019). In addition, CD3+ cell densities in the tumor and stroma were significantly higher in IM tumors (P = 0.002 and P < 0.001), while lower levels were found in M tumors (P = 0.005, P = 0.002). Similarly, stromal CD20+ levels were higher in IM tumors (P = 0.008) and lower in M tumors (P = 0.006), suggesting a more immunosuppressive TME in the M subtype. CD8+ cells levels were not significantly different between subtypes. Conclusions: These preliminary results show relevant differences in the pCR rates among TNBC subtypes, to be confirmed on a larger series of patients and further suggesting a substantial TNBC heterogeneity regarding treatment response. Of note, preliminary mIF results suggest a differential role of the immune response across molecular subtypes. Additional analyses integrating mIF and genomic data are currently ongoing. Funding: IMI2 JU grant agreement 821558, supported by EU’s Horizon 2020 and EFPIA. Citation Format: Andrea Joaquin Garcia, Mattia Rediti, Abdelkader Benyagoub, Stéphanie Tissot, Sylvie Rusakiewicz, Robin Liechti, Flavia Marzetta, Nicolas Penel, Julio Oliveira, Jean-Charles Goeminne, Pierre Fournel, Andreia Capela, Xiaoxiao Wang, Delphine Vincent, Françoise Rothe, Marie Morfouace, Henoch Hong, Donald Jackson, Christos Sotiriou, Laurence Buisseret. Pathologic complete response rate across triple negative breast cancer subtypes in the IMMUcan study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4522.