Abstract 3430
Background
Immune checkpoint inhibition monotherapy has shown no efficacy in microsatellite-stable (MSS) CRC. Combination strategies are being studied to increase the immunogenicity of this cold tumor. Humanized mice are promising models to evaluate immunotherapy combinations and their effects in the engrafted human immune system.
Methods
3 MSS CRC patient-derived xenografts were injected subcutaneously into 68 mice previously humanized through CD34+ cord blood-derived hematopoietic cell transplantation. Mice were allocated into 4 equivalent groups based on human chimerism detected in the blood and subsequently treated with anti-PD-1 therapy and/or multi-tyrosine kinase inhibition. At harvest, flow cytometry immune data from the lymph nodes (LN), the spleen (SP) and tumor-infiltrating lymphocytes (TIL) were analyzed. Mice were classified according to the specific growth rate (SGR, % volume / day) of their tumor/s into R (under median SGR) vs non-R (over median SGR).
Results
50 mice were considered either R (26) or non-R (24). In the peripheral immune organs (LN and SP), the total number of immune cells was similar between R and non-R mice. However, a higher percentage of human and T cells was found in the SP of R mice. Interestingly, the percentage of B cells was higher in the LN and SP of non-R mice. In contrast, in the tumor, an increased number of human cells (mostly T cells) was found in R mice. Notably, CD8+ T cells were significantly higher among TILs. A linear regression analysis was performed, and the number of human and T (CD4+ and CD8+) cells in the tumor significantly decreased (P<.001for all of them) with an increasing tumor SGR.Table: 1904P
Periphery % cells | Tumor nº cells / g | ||||||||
---|---|---|---|---|---|---|---|---|---|
LN | SP | R | Non-R | P* | |||||
R | Non-R | P | R | Non-R | P | ||||
Human cells T cells CD4 CD8 B cells | 95 78 77 23 10 | 94 76 79 20 16 | .17 .40 .54 .51 .016 | 38 81 77 23 10 | 23 71 75 24 21 | .009 .017 .68 .72 .001 | 57648 47794 38094 9210 443 | 22745 18191 14852 3052 555 | .036 .052 .069 .012 .079 |
T-test on Ln-transformed values
Conclusions
Different immune responses were observed both in the periphery and in the tumor between R and non-R mice. The humanized mouse model appears to be a valid model to evaluate immunotherapy combinations for MSS CRC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University of Colorado, Anschutz Medical Campus.
Funding
University of Colorado, Anschutz Medical Campus.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5822 - Greek nursing students experience facing death in clinical practice
Presenter: Maria Dimoula
Session: Poster Display session 3
Resources:
Abstract
2866 - HOPEVOL: Hospice care appropriate to the wishes and needs of patients in the palliative terminal phase.
Presenter: Merel van Klinken
Session: Poster Display session 3
Resources:
Abstract
829 - Mindfulness-based stress reduction in early palliative care for advanced cancer patients : an italian single-centre study. MINDEEP
Presenter: Emilia Gianotti
Session: Poster Display session 3
Resources:
Abstract
2702 - Optimising Inpatient Oncology Care
Presenter: Lisa Judge
Session: Poster Display session 3
Resources:
Abstract
1527 - Analysis on the Implementation Results of Family Sickbed for Oncology Patients in Dongshi Township Health Centers from 2015 to 2017
Presenter: Yayu Huang
Session: Poster Display session 3
Resources:
Abstract
2054 - Exploring needs for palliative care and quality of life for oncology patients with advanced disease who undergo radiotherapy
Presenter: Foteini Antonopoulou
Session: Poster Display session 3
Resources:
Abstract
5605 - Cytotoxic contamination in cancer care settings – Risks and safety awareness among cancer nurses
Presenter: Sandra Lundman Vikberg
Session: Poster Display session 3
Resources:
Abstract
5769 - Understanding Chemotherapy - group education sessions prior to commencing chemotherapy
Presenter: Aileen McHale
Session: Poster Display session 3
Resources:
Abstract
2620 - Estimation of HPQ-based absenteeism and presenteeism in cancer patients via ResearchKit
Presenter: Shunsuke Kondo
Session: Poster Display session 3
Resources:
Abstract
4705 - Identifying falls-related variables and risk factors in hospitalised cancer patients
Presenter: Maria Montserrat Martí Dillet
Session: Poster Display session 3
Resources:
Abstract