{"id":2270,"date":"2020-12-20T12:34:08","date_gmt":"2020-12-20T12:34:08","guid":{"rendered":"https:\/\/bibliography.nanobiotix.com\/?p=2270"},"modified":"2020-12-20T12:34:08","modified_gmt":"2020-12-20T12:34:08","slug":"2020-sitc-nbtxr3-tcr-repertoire","status":"publish","type":"post","link":"https:\/\/bibliography.nanobiotix.com\/fr\/2020-sitc-nbtxr3-tcr-repertoire\/","title":{"rendered":"2020 \u2013 SITC \u2013 TCR Repertoire"},"content":{"rendered":"<section class=\"wpb-content-wrapper\"><p>[vc_row padding_top=\u00a0\u00bb0&Prime; padding_bottom=\u00a0\u00bb0&Prime; section_container_layout=\u00a0\u00bbfull-width\u00a0\u00bb remove_horizontal_padding=\u00a0\u00bbyes\u00a0\u00bb module_type=\u00a0\u00bbbg-color\u00a0\u00bb gutter_size=\u00a0\u00bbyes\u00a0\u00bb equal_height=\u00a0\u00bbyes\u00a0\u00bb bg_color=\u00a0\u00bb#28282e\u00a0\u00bb][vc_column][vc_row_inner padding_top=\u00a0\u00bb0&Prime; padding_bottom=\u00a0\u00bb0&Prime; gutter_size=\u00a0\u00bbyes\u00a0\u00bb equal_height=\u00a0\u00bbyes\u00a0\u00bb][vc_column_inner column_paddings=\u00a0\u00bb105&Prime; column_position_vertical=\u00a0\u00bbmiddle\u00a0\u00bb column_min_height=\u00a0\u00bb700&Prime; column_min_height_sm=\u00a0\u00bb400&Prime; column_min_height_xs=\u00a0\u00bb350&Prime; module_type=\u00a0\u00bbbg-image\u00a0\u00bb bg_image=\u00a0\u00bb102&Prime; mask_fx=\u00a0\u00bbyes-mask\u00a0\u00bb mask_color_mode=\u00a0\u00bbpalette\u00a0\u00bb mask_bg_color_palette=\u00a0\u00bbmain-mask\u00a0\u00bb animation_fx=\u00a0\u00bbyes-animation\u00a0\u00bb animation_delay=\u00a0\u00bb200&Prime; animation_offset_scroll_down=\u00a0\u00bb90&Prime; width=\u00a0\u00bb1\/2&Prime; animation_in=\u00a0\u00bbfadeInUp\u00a0\u00bb][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][az_box_icons box_icon_title=\u00a0\u00bbAuthors\u00a0\u00bb box_icon_color_mode=\u00a0\u00bbon-the-fly\u00a0\u00bb icon_visibility=\u00a0\u00bbyes-icon\u00a0\u00bb icon_type=\u00a0\u00bbfont\u00a0\u00bb icon=\u00a0\u00bbfa fa-edit\u00a0\u00bb icon_color_mode=\u00a0\u00bbon-the-fly\u00a0\u00bb icon_size=\u00a0\u00bb50&Prime; box_icon_color=\u00a0\u00bb#ffffff\u00a0\u00bb icon_color=\u00a0\u00bb#ffffff\u00a0\u00bb]Audrey Darmon, Ping Zhang, S\u00e9bastien Paris<br \/>\n<span class=\"notes\"><br \/>\nNanobiotix, 60 rue de Wattignies 75012 Paris, France<br \/>\n<\/span>[\/az_box_icons][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][\/vc_column_inner][vc_column_inner column_paddings=\u00a0\u00bb105&Prime; column_position_vertical=\u00a0\u00bbmiddle\u00a0\u00bb module_type=\u00a0\u00bbbg-color\u00a0\u00bb animation_fx=\u00a0\u00bbyes-animation\u00a0\u00bb animation_delay=\u00a0\u00bb300&Prime; animation_offset_scroll_down=\u00a0\u00bb90&Prime; width=\u00a0\u00bb1\/2&Prime; bg_color=\u00a0\u00bb#ffffff\u00a0\u00bb animation_in=\u00a0\u00bbfadeInUp\u00a0\u00bb][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][az_box_icons box_icon_title=\u00a0\u00bbSummary\u00a0\u00bb icon_visibility=\u00a0\u00bbyes-icon\u00a0\u00bb icon_type=\u00a0\u00bbfont\u00a0\u00bb icon=\u00a0\u00bbaz-icon az-icon-layers2&Prime; icon_color_mode=\u00a0\u00bbon-the-fly\u00a0\u00bb icon_color=\u00a0\u00bb#28282e\u00a0\u00bb icon_size=\u00a0\u00bb50&Prime;]For decades, radiotherapy (RT) has been a cornerstone of cancer treatment. Currently, approximately 50% of cancer patients will be treated with RT. Beyond the ability of RT to produce free radicals and to generate single and double-strand breaks in DNA, triggering cell death, preclinical and clinical studies have demonstrated that RT can have immunomodulatory effects. For example, RT can stimulate MHC class I expression on cancer cells, induce immunogenic cell death (ICD), and activate expression of various pro- and anti-inflammatory cytokines and adhesion molecules, allowing recruitment and activation of both innate and adaptive immune cells into the tumor. Unfortunately, RT rarely produces a sustained anti-tumor response as immune escape frequently occurs with tumor recurrence. Moreover, the so-called \u2018abscopal effect\u2019 which corresponds to reduction of metastatic burden outside the irradiated area is rarely observed after RT. Finally, the maximum dose of irradiation is limited because of toxicity to surrounding healthy tissues.<\/p>\n<p>The high electron density of functionalized hafnium oxide nanoparticles (NBTXR3) allows a high probability of interaction with incoming ionizing radiation, increasing energy dose deposit within cells. We have previously reported in nonclinical studies the ability of RT-activated NBTXR3 (NBTXR3+RT) to increase cancer cell destruction as well as better control of treated tumor growth through this physical mode of action leading, compared to RT alone. Furthermore, NBTXR3+RT demonstrated clinically meaningful benefit for patients with locally advanced Soft Tissue Sarcoma compared to RT alone, in the randomized controlled phase II\/III Act.in.Sarc study (NCT02379845).<\/p>\n<p>To explore the impact of NBTXR3+RT on the anti-tumor immune response, we used CT26 mouse colorectal cancer cells to perform a series of abscopal assays in immunocompetent mice. We showed that NBTXR3+RT can generate a significant abscopal effect along with a substantial increase of CD8+ T cell infiltrates both in treated and untreated tumors, compared to RT alone. We showed that this distant effect was fully dependent on CD8+ T cells, as their depletion completely abolished the abscopal effect. To better understand how NBTXR3+RT treatment could generate this abscopal effect, we compared the TCR repertoire of treated and untreated tumors for the different conditions. This analysis revealed that NBTXR3+RT was able to broaden clonal diversity in both treated and untreated tumors, compared to RT alone. This indicates that NBTXR3+RT has the ability to transform the tumor into a in situ vaccine more efficiently than RT alone and could have important implications for the use of NBTXR3+RT in combination with immunotherapy.<br \/>\n[\/az_box_icons][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][\/vc_column_inner][\/vc_row_inner][\/vc_column][\/vc_row]<\/p>\n<\/section>","protected":false},"excerpt":{"rendered":"<p>For decades, radiotherapy (RT) has been a cornerstone of cancer treatment. Currently, approximately 50% of cancer patients will be treated with RT. Beyond the ability of RT to produce free radicals and to generate single and double-strand breaks in DNA, triggering cell death, preclinical and clinical studies have demonstrated that RT can have immunomodulatory effects. For example, RT can stimulate MHC class I expression on cancer cells, induce immunogenic cell death (ICD), and activate expression of various pro- and anti-inflammatory cytokines and adhesion molecules, allowing recruitment and activation of both innate and adaptive immune cells into the tumor. [\u2026]<\/p>\n","protected":false},"author":1,"featured_media":2276,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[182,184,666],"tags":[499,629],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2270"}],"collection":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/comments?post=2270"}],"version-history":[{"count":1,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2270\/revisions"}],"predecessor-version":[{"id":2306,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2270\/revisions\/2306"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media\/2276"}],"wp:attachment":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media?parent=2270"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/categories?post=2270"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/tags?post=2270"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}