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The CD93 pathway and melanoma therapy

Award Number: R01CA258302
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/03/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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The CD93 pathway and melanoma therapy - PROJECT SUMMARY/ABSTRACT Immune checkpoint blocker therapy has recently greatly improved survival of patients with late- stage melanoma. However, about 2/3 of patients do not benefit from this therapy. One of main hurdles is that many melanoma tissues lack effector CD8+ T cells. The immature and dysfunctional blood vessels actively limit T cell infiltration. Recently vascular normalization has been demonstrated to be able to facilitate effector immune cell infiltration and to improve cancer immunotherapy. a novel pathway in the IGFBP7/CD93 interaction, both of which are selectively upregulated in tumor vasculature. Our preliminary study indicates that disrupting this interaction in vivo normalizes tumor vessels to reduce hypoxia and improve tumor perfusion in mouse melanoma models. Our examination of tumor tissues reveals that blockade of this pathway could reinvigorate tumor blood vessels to promote T cell infiltration while limit myeloid-derived suppressor cells in the tumor. Here we hypothesize that upregulation of this pathway contributes to the tumor vascular abnormality and targeting this pathway will offer a novel approach to facilitate melanoma immunotherapy. We will dissect how this pathway is induced in the tumor and consequently leads to tumor vascular dysfunction and then tumor outgrowth. The mechanisms by which CD93 regulates immune cell infiltration, as well as its expression causing resistance to anti-PD1 therapy, will be evaluated. By the completion of these studies, we will gain insight into the biological role of this pathway in the cancer microenvironment of melanoma and, more importantly, provide a new strategy of promoting immunotherapy in melanoma. Our studies uncovered


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $355,706 )
2025	2025	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	000	4	11/21/2024	NON-COMPETING CONTINUATION	$320,136
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	001	4	6/4/2025	NON-COMPETING CONTINUATION	$35,570
														Subtotal = $355,706

Issue Date FY: 2024 ( Subtotal = $337,922 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	001	3	4/22/2024	NON-COMPETING CONTINUATION	$17,786
2024	2024	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	000	3	11/30/2023	NON-COMPETING CONTINUATION	$320,136
														Subtotal = $337,922

Issue Date FY: 2023 ( Subtotal = $348,592 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	000	2	12/1/2022	NON-COMPETING CONTINUATION	$320,136
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	001	2	3/17/2023	NON-COMPETING CONTINUATION	$28,456
														Subtotal = $348,592

Issue Date FY: 2022 ( Subtotal = $355,706 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	000	1	12/3/2021	NEW	$355,706
														Subtotal = $355,706

Grand Total All Awards = $1,397,926

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The CD93 pathway and melanoma therapy

Award Number: R01CA258302

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/03/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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