Distinct Responsiveness of Tumor-Associated Macrophages to Immunotherapy of Tumors with Different Mechanisms of Major Histocompatibility Complex Class I Downregulation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F21%3A10431294" target="_blank" >RIV/00216208:11310/21:10431294 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OHRotmS1vP" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OHRotmS1vP</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers13123057" target="_blank" >10.3390/cancers13123057</a>

Result language

angličtina

Original language name

Distinct Responsiveness of Tumor-Associated Macrophages to Immunotherapy of Tumors with Different Mechanisms of Major Histocompatibility Complex Class I Downregulation

Original language description

Simple Summary Tumor-associated macrophages (TAMs) are one of the major cell subpopulations in the tumor microenvironment (TME) where they can either be pro-tumorigenic or contribute to an anti-tumor immunity. The TME and TAM phenotype were analyzed after combined immuno-therapy (IT) in tumor models characterized by distinct expression of major histocompatibility class I complex (MHC-I) molecules, i.e., tumors induced with TC-1 (MHC-I-proficient), TC-1/A9 (reversibly downregulated), and TC-1/dB2m (irreversibly downregulated) cells. We found out that combined IT highly activated immune reactions in the TME of TC-1 and TC-1/A9 tumors, but the TME of TC-1/dB2m tumors remained almost unchanged. Correspondingly, TAMs from TC-1/A9 tumors were able to destroy tumor cells in vitro, while TAMs isolated from TC-1/dB2m tumors showed profoundly decreased cytotoxicity. Hence, various capabilities of TAMs in tumors with distinct expression of MHC-I molecules should be considered when applying IT, particularly IT focused on TAMs. Tumor-associated macrophages (TAMs) plentifully infiltrate the tumor microenvironment (TME), but their role in anti-tumor immunity is controversial. Depending on the acquired polarization, they can either support tumor growth or participate in the elimination of neoplastic cells. In this study, we analyzed the TME by RNA-seq and flow cytometry and examined TAMs after ex vivo activation. Tumors with normal and either reversibly or irreversibly decreased expression of major histocompatibility complex class I (MHC-I) molecules were induced with TC-1, TC-1/A9, and TC-1/dB2m cells, respectively. We found that combined immunotherapy (IT), composed of DNA immunization and the CpG oligodeoxynucleotide (ODN) ODN1826, evoked immune reactions in the TME of TC-1- and TC-1/A9-induced tumors, while the TME of TC-1/dB2m tumors was mostly immunologically unresponsive. TAMs infiltrated both tumor types with MHC-I downregulation, but only TAMs from TC-1/A9 tumors acquired the M1 phenotype upon IT and were cytotoxic in in vitro assay. The anti-tumor effect of combined IT was markedly enhanced by a blockade of the colony-stimulating factor-1 receptor (CSF-1R), but only against TC-1/A9 tumors. Overall, TAMs from tumors with irreversible MHC-I downregulation were resistant to the stimulation of cytotoxic activity. These data suggest the dissimilarity of TAMs from different tumor types, which should be considered when utilizing TAMs in cancer IT.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/GA19-00816S" target="_blank" >GA19-00816S: Experimental cancer immunotherapy, tumor heterogeneity, and overcoming tumor immune escape</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cancers

ISSN

2072-6694

e-ISSN

—

Volume of the periodical

13

Issue of the periodical within the volume

12

Country of publishing house

CH - SWITZERLAND

Number of pages

23

Pages from-to

3057

UT code for WoS article

000666419800001

EID of the result in the Scopus database

2-s2.0-85108087016