176P - Multiplex-immunoflourescence spatial patterns to predict triple-negative breast cancer molecular subtypes in the IMMUcan study

Background

IMMUcan (SPECTA NCT02834884) is a European initiative to profile the tumor microenvironment (TME) for a better understanding of immune-tumor interactions. Here, we explored the association between distinct molecular phenotypes and spatial TME patterns in the prospective neoadjuvant IMMUcan TNBC cohort.

Methods

From a preliminary cohort of 132 patients, matched baseline RNA-seq and multiplex immune fluorescence (mIF) data were available for 66 cases. The mIF panel included CD8, PD1, PD-L1, granzyme B (GB), Ki67 and CK markers. Spatial TME patterns were defined by a graph-based approach detecting densely populated regions of tumor cells and their immune neighbors. TNBC molecular subtypes were derived from RNA-seq as described by Bareche et al. Area Under the Curve (AUC) was used to evaluate the accuracy of spatial patterns to predict TNBC subtypes.

Results

A total of eight distinct clusters were identified across the 66 samples, each exhibiting a specific spatial distribution of mIF markers. Two of the clusters showed high performance in predicting immunomodulatory phenotype (AUC: 0.72, 0.71, respectively). These clusters presented elevated densities of CD8+, CD8+/GB+, and CD8+/Ki67+ cells, consistent with CD8+ effector T cells. In addition, a cluster characterized by tumor cells correlated with the luminal androgen-receptor phenotype (AUC: 0.91). The basal-like phenotype was represented by a cluster exhibiting high levels of Ki67+ tumor cells (AUC: 0.61). A distinct cluster displaying an intermediate proportion of Ki67+ tumor cells was observed as well, representing the mesenchymal subtype (AUC: 0.69).

Conclusions

These preliminary analyses revealed the presence of informative spatial patterns populating mIF data, linked to the distribution of immune/tumor markers within the TME of TNBC. Of note, these spatial patterns were associated with distinct RNA-seq TNBC subtypes. These findings suggest the predictive power of mIF markers as a potential surrogate to discern TNBC heterogeneity. Consequently, these observations, if confirmed by further validations, could facilitate the implementation of treatment strategies tailored to the TNBC molecular subtypes.

Legal entity responsible for the study

EORTC.

Funding

IMI2 JU grant agreement 821558, supported by EU’s Horizon 2020 and EFPIA.

Disclosure

M. Morfouace: Financial Interests, Personal, Full or part-time Employment: Merck. H.S. Hong: Other, Personal, Full or part-time Employment: Merck. M. Cesaroni: Financial Interests, Personal, Full or part-time Employment: Sanofi. 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. 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, Research Grant, Research Grant for an investigator initiated trial: Astra Zenaca; Non-Financial Interests, Personal, Principal Investigator: iTeos Therapeutics; Non-Financial Interests, Personal, Member: EORTC, BSMO. All other authors have declared no conflicts of interest.