40P - Bioinformatic evaluation of the transcriptomic and immunologic profile of prostate tumors with high expression of kallikrein-2

Background

Identification of tumor associated antigens (TAAs) expressed on the cell membrane of tumoral cells is a main goal in cancer research. T cell engagers (TCE) are bi-specific antibodies that engage a TAA with an effector T cell receptor mainly CD3. Kallikrein-2 (KLK2) is a surface protein for which TCE are currently in clinical development. In our study we explore genomic correlates and the transcriptomic and immunologic profile of tumors with high expression of KLK2.

Methods

Primary prostate cancer data was downloaded from TCGA to study transcripts up or down regulated when high expression of KLK2 was present. Tumor Estimation Resource (TIMER) platform was employed to investigate the association between high expression of KLK2 and immune cell populations. Correlations between transcripts were performed using Spearman’s correlation test.

Results

KLK2 was specifically upregulated in prostate cancer compared with other solid tumors and normal tissue (tumor 5956.5 TPM versus normal 4175.26 TPM). KLK2 expression did not associate with the presence of any immune cell population either innate or adaptive cells including CD8+ (Rho = 0.339, p = 1.03E-12), CD4+ (Rho = -0.244, p = 4.56E-07), B cells (Rho = 0.047, p = 0.332), neutrophils (Rho = -0.139, p =0.004), dendritic cells (Rho =-0.152, p = 0.001), or macrophages (Rho= 0.074, p =0.128). No clear association was observed for any biomarker of T cell activation including CD8A, CD8B, GZMA, GZMb or PRF1, or an additional battery including more than 40 additional genes linked with T cell cytotoxic. A mild correlation was observed between high expression of KLK2 and TMPRSS2 (Rho = 0.481, p = 1,68E-11). Protein protein interaction analysis showed interactions with AR, KLK3, IGF1, IGFBP3 (PPI enrichment p-value: 4.51e-07), among others. Co- upregulated surface proteins include TMEFF2, OR51E2, CD320 and FAM17AB; and nonsurface proteins: RDH11, FX4D3, SSR4 and NDUFA13. None of them were specifically expressed in tumoral cells or associated with biochemical (PSA) relapse.

Conclusions

KLK2 is highly and exclusively expressed in prostate cancer mainly in inmune desert tumors. Future studies should be performed in other clinical scenarios like in androgen resistant prostate tumors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

V. Moreno Garcia: Financial Interests, Personal, Advisory Board: BMS, Janssen, Roche, Basilea, Bayer, AstraZeneca; Financial Interests, Personal, Full or part-time Employment: START; Financial Interests, Institutional, Local PI, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer BeiGene BioInvent International AB, BMS, Boehringer Ingelheim, Boston, Celgene, Daiichi Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith: Multiple. E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Amunix, Anaveon, AstraZeneca, BMS, Janssen, MonTa, MSD, Nanobiotix, Nouscom, Novartis, Servier, TargImmune, T-knife, Chugai, Elevation Oncology, Ellipses Pharmacy, SyneosHealth, Genmab, Diaccurate; Financial Interests, Personal, Invited Speaker: OncoDNA, PharmaMar, Roche/Genentech; Financial Interests, Personal, Full or part-time Employment, Director, Clinical Research: HM Hospitales Group; Financial Interests, Personal, Full or part-time Employment, Medical Oncologist. Clinical Investigator. Director, Clinical Research: START Madrid - CIOCC (Centro Integral Oncológico Clara Campal); Financial Interests, Personal, Member of Board of Directors, External Independent member of Board of Directors: PharmaMar; Financial Interests, Personal, Ownership Interest: START, Oncoart Associated; Financial Interests, Personal, Steering Committee Member, Member of Data Monitoring Committee: BeiGene, Sanofi, Merus; Financial Interests, Personal, Steering Committee Member: Novartis; Non-Financial Interests, Other, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) non-for-profit Foundation; Non-Financial Interests, , Advisory Role: PsiOxus; Non-Financial Interests, Other, Chair of the Independent Data Monitoring Committee: EORTC IDMC; Non-Financial Interests, Member of Board of Directors, Non-for-profit Foundation, trustee member: Non-for-profit Foundation PharmaMar; Non-Financial Interests, Advisory Role, Non-for-profit foundation: CRIS Cancer Foundation, non-for-profit ; Non-Financial Interests, Member: ASCO, ESMO, SEOM, EORTC. All other authors have declared no conflicts of interest.