257P - Spatial predictors of pathologic complete response to neoadjuvant chemotherapy using imaging mass cytometry in the IMMUcan TNBC cohort

Background

IMMUcan is a European initiative to profile the tumor microenvironment to better understand immune-tumor interactions, and their impact of current therapeutic interventions. Here, we explored the association between spatial imaging mass cytometry (IMC) patterns, molecular TNBC subtypes, and response to neoadjuvant chemotherapy in the IMMUcan triple-negative breast cancer (TNBC) cohort.

Methods

IMC data were available for 95 patients, 73 having matched baseline RNA-seq data. Pathological complete response (pCR) status was available for 86 patients. The IMC panel included 40 markers. Cellular neighborhoods (CNs) were defined as described by Schürch et al. Cell (2020). TNBC molecular subtypes were derived from RNA-seq as described by Bareche et al. Ann Oncol (2018). The association of continuous variables with pCR was evaluated using logistic regression controlling for tumor size, grade, and nodal status.

Results

Among 25 cell types identified with IMC, mural cells (endothelial, fibroblasts, muscle cells) were associated with residual disease, while higher levels of specific immune cells such as CD8+/Gzmb+, CD8+/Ki67+, and CD4+/Ki67+ showed a trend toward improved pCR rates. As expected, the immunomodulatory TNBC subtype was enriched for immune cells, including CD4, CD8, NK, Treg and plasma cells. Further analyses identified 10 CNs characterized by the presence of different cell types, each with its own predictive value. Specifically, a spatial interface between mural cells and immune cells, including macrophages and dendritic cells, was associated with a lack of pCR (OR: 0.64; False discovery rate [FDR] = 0.04). Conversely, a spatial interface involving plasma cells and NK cells in contact with tumor areas significantly predicted pCR (OR: 3.5; FDR = 0.03), suggesting the presence of cytotoxic activity against tumor cells.

Conclusions

Our findings emphasize the importance of analyzing spatial patterns to predict pCR, a feature not observable when evaluating cell density analysis alone. These results demonstrate the value of understanding complex spatial interactions among cells to enhance predictive accuracy and improve therapeutic strategies.

Clinical trial identification

SPECTA NCT02834884.

Editorial acknowledgement

Legal entity responsible for the study

IMMUcan consortium.

Funding

The IMMUcan (SPECTA NCT02834884) project has received funding from IMI2 JU grant agreement 821558, supported by EU’s Horizon 2020 and EFPIA. The SPECTA platform is supported by Alliance Healthcare, a member of the AmerisourceBergen Group.

Disclosure

N. Penel: Financial Interests, Institutional, Research Grant, Research grant for clinical trials in sarcoma filed: BAYER HealthCare. J. Oliveira: Other, Institutional, Other, P.CCC. : Centro Compreensivo de Cancro do Porto (TeamUp4Cancer), funded by EU grant NORTE-01-0145-FEDER-072678: P.CCC. : Centro Compreensivo de Cancro do Porto (TeamUp4Cancer), funded by EU grant NORTE-01-0145-FEDER-072678. C. Sotiriou: Financial Interests, Institutional, Advisory Board: Astellas, Vertex, Seattle Genetics, AMGEN, INC, Merck & Co; Financial Interests, Personal, Advisory Board: Cepheid, Puma; Financial Interests, Personal, Invited Speaker: Eisai, Prime oncology, Teva; Financial Interests, Institutional, Other, Travel: Roche; Financial Interests, Institutional, Other, Internal speaker: Genentech; Financial Interests, Personal, Other, Regional speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Personal, Advisory Board, Stock options: Signatur Biosciences. L. Buisseret: Financial Interests, Institutional, Advisory Board: Domain Therapeutics; Financial Interests, Institutional, Other, Steering Committee: iTEOS Therapeutics; Financial Interests, Personal, Other, writing of clinical cases: Mirrors of Medicine; Financial Interests, Institutional, Other, Travel grant: GILEAD; Financial Interests, Institutional, Other, travel grant: AstraZeneca; Financial Interests, Institutional, Research Grant, Research Grant for an investigator initiated trial: Astra Zenaca; Non-Financial Interests, Principal Investigator: iTeos Therapeutics; Non-Financial Interests, Member, Member of the Breast Group and IMMUcan consortium: EORTC; Non-Financial Interests, Member: BSMO, ASCO. All other authors have declared no conflicts of interest.