28P - Immune profiling of colorectal cancer in CANScript™ platform deciphers heterogeneity of tumor microenvironment and immune check point phenotype status

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Manjusha Biswas
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors M. Biswas1, B. Tewary1, D. Mehrotra1, B. Majumder1, P.K. Majumder2
  • 1Molecular Pathology, Mitra Biotech Pvt. Ltd, 560099 - Bangalore/IN
  • 2Molecular Pathology, Mitra Biotech Pvt. Ltd, 01801 - Woburn/US

Abstract

Aim/Background

Delineation of intra-tumor immune microenvironment in a dynamic spatiotemporal setting is being appreciated owing to its clinical relevance in many cancer indications including Colorectal Cancer (CRC). CRC is one of the leading causes of cancer related mortalities, represents a highly complex microenvironment wherein multiple dysregulated immune phenotypes have the capacity to explain response/nonresponse to a particular treatment at personalized level. In order to understand the role functional immune phenotypes we evaluated a cohort of 35 tumors from CRC patients.

Methods

We have analysed diverse range of immune cells present in the tumors and their subsequent enrichment within the tumour, when co-cultured with patient’s own tumor in multidimensional CANScript™ functional platform (Majumder B et al. Nat Commun, 6:6169:1-14 (2015). Markers spanning functionally diverse immune phenotypes (for e.g., CD8, CD45, CD45RO, FOXP3, CD68, PDL1, CTLA4 and pro-inflammatory cytokines (such as IL6, IL8 etc.) were quantified based on their percent positivity and intensities.

Results

Data showed heterogeneous expression patterns of these markers irrespective of tumor stages and clinical variables. However, further analysis of their cross talk using gene expression and targeted IHC profiling led to the identification of immune signatures indicative of differential immune checkpoint phenotypes and M1-M2/signalling profiles. This data suggest that CANScriptTM platform might be used to understand the biology and underlying mechanism of action of immune checkpoint inhibitors.

Conclusions

Functional validation of this system-biology approach in CANscript explant model confirmed that different patient tumors selectively respond to different immunomodulator agents. Together these findings suggest the utility of immune profiling for personalization of treatment decision in colorectal cancer where existing therapies often show response failure.

Clinical trial identification

Not Applicable

Legal entity responsible for the study

N/A

Funding

Mitra Biotech Pvt. Ltd., Bangalore & Mitra Biotech, Woburn, MA, USA

Disclosure

P.K. Majumder: Employee of Mitra Biotech, Woburn, MA, USA. M. Biswas, B. Tewary, D. Mehrotra, B. Majumder: Employees of Mitra Biotech’s affiliate, Bangalore, India.