Abstract 3751
Background
Designated tumor infiltrating lymphocytes (TIL) within tumor microenvironment (TME) comprised of both regulatory cells and effector cells, and their interaction with tumor cells account for the immune escape and immunosurveillance mechanisms respectively. The number and location of CD8+ tumor infiltrating lymphocytes (TILs) are the measures of immune response and carries prognostic significance and predictive potential in the era of immuno-oncology. The present study was an attempt to find the relation between the treatment response and the spatio-temporal separation of tumor infiltrating CD8+ T-cells and HER2/neu+ tumor cells in breast cancer TME.
Methods
In this study, a total of 7 breast cancer patients were enrolled and surgically removed fresh tumor tissues were evaluated for the baseline HER2/neu and CD8 expression by immunohistochemistry (IHC) using dual stain (duplex IHC). The tumor tissues were also tested for the response to HER2 blocker in a novel humanized ex vivo platform that preserves tumour microenvironment using tumour explants, maintained in defined tumour grade-matched matrix support and autologous patient serum.
Results
Tumors responded to HER2 blockade had a majority of the CD8+ T cells (60-80%) concentrated around the HER2/neu+ tumor area (within 50-100µm). While, the non-responding tumors had significantly lesser number of the CD8+T cells (20-40%) proximal to HER2/neu+ zone compared to the responders. The present study indeed delineated a preferential spatial relationship of tumor infiltrating CD8+ cells in HER2/neu+ tumor region especially for the recognition of tumor antigen, cross presentation and tumor cell killing.
Conclusions
Assessment of distribution pattern of effector cells surrounding tumor area had a correlation on the efficacy of HER2 inhibition. It warrants validation in the larger cohort of patient tumors to underpin its clinical relevance for possible immunotherapies like combination of check point inhibitors with HER2/neu blocker and others. Identification of other co-stimulatory and pathway molecules on the tumors not responded to HER2 blocker is being studied to understand the mechanism of resistance.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Mitra RxDx Inc.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2831 - Interleukin-6 as a Predictive Marker for Early Response to Induction Chemotherapy in Acute Myeloblastic Leukaemia
Presenter: Salah Khallaf
Session: Poster Display session 1
Resources:
Abstract
6014 - Impact of FLT3-ITD mutation on post-transplant outcome of adult AML is modified by the concomitant NPM1 mutation and pre-transplant remission status: A report from Taiwan Bone Marrow Transplant Registry (TBMTR)
Presenter: Su-peng Yeh
Session: Poster Display session 1
Resources:
Abstract
2914 - Efficacy endpoints studied in clinical trials for early-onset leukaemia
Presenter: Dylan Said
Session: Poster Display session 1
Resources:
Abstract
4691 - High triglyceride is a major risk factor of DIC and differentiation syndrome in acute promyelocytic leukemia
Presenter: Tomohiro Yamakawa
Session: Poster Display session 1
Resources:
Abstract
4395 - DREAMM 4: A Phase I/II single-arm open-label study to explore safety and clinical activity of belantamab mafodotin (GSK2857916) administered in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM)
Presenter: Suzanne Trudel
Session: Poster Display session 1
Resources:
Abstract
2808 - A Phase 1 Study of HMPL-523, a Selective Oral Anti-Spleen Tyrosine Kinase Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Nathan Fowler
Session: Poster Display session 1
Resources:
Abstract
4403 - A Phase 1 Study of HMPL-689, a Selective Oral Phosphoinositide 3-Kinase-Delta Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Jonathon Cohen
Session: Poster Display session 1
Resources:
Abstract
3357 - A global patient-driven Facebook study in a very rare sarcoma: Health-related quality of life in Epithelioid Hemangioendothelioma (EHE) patients
Presenter: Marije Weidema
Session: Poster Display session 1
Resources:
Abstract
2475 - Qualitative study of patients’ experiences of living with and beyond a soft tissue sarcoma diagnosis: the impact of sarcoma specialist services
Presenter: Ana Martins
Session: Poster Display session 1
Resources:
Abstract
2640 - Health-related quality of life issues of patients affected by desmoid-type fibromatosis; experiences from two countries
Presenter: Milea Timbergen
Session: Poster Display session 1
Resources:
Abstract