Mucosal Imprinting of Vaccine-Induced CD8 ⁺ T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors

Abstract

Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. We showed that the growth of orthotopic head and neck or lung cancers was inhibited when a cancer vaccine was delivered by the intranasal mucosal route but not the intramuscular route. This antitumor effect was dependent on CD8+ T cells. Indeed, only intranasal vaccination elicited mucosal-specific CD8+ T cells expressing the mucosal integrin CD49a. Blockade of CD49a decreased intratumoral CD8+ T cell infiltration and the efficacy of cancer vaccine on mucosal tumor. We then showed that after intranasal vaccination, dendritic cells from lung parenchyma, but not those from spleen, induced the expression of CD49a on cocultured specific CD8+ T cells. Tumor-infiltrating lymphocytes from human mucosal lung cancer also expressed CD49a, which supports the relevance and possible extrapolation of these results in humans. We thus identified a link between the route of vaccination and the induction of a mucosal homing program on induced CD8+ T cells that controlled their trafficking. Immunization route directly affected the efficacy of the cancer vaccine to control mucosal tumors.

Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model

“…This was a larger percentage compared with the value reported in a previous study (39), where a value of 16.6% CD8 + T lymphocytes was reported for an autologous lysate-based vaccine, which was considered to be clinically successful. The strong statistical correlation between the mean survival time and CD8a + population size in the present study (r= 0.985) indicates that cytotoxic T-lymphocytes may be a pivotal element in the vaccine-induced antitumour immune response, which is in agreement with data from the literature (40)(41)(42)(43)(44).…”

Intravenous Injection of MVA Virus Targets CD8+ Lymphocytes to Tumors to Control Tumor Growth upon Combinatorial Treatment with a TLR9 Agonist

“…The route of immunization can affect the subsequent migratory capacity of primed antigen-specific T cells (10)(11)(12). Therefore, we compared the s. These data indicate a therapeutic advantage of i.v.…”

“…For example, the implantation of colorectal adenocarcinoma cells under the skin would not recreate a tumor microenvironment reflecting that of spontaneous colon cancer. In addition, there is now evidence to suggest that the immunization route influences the subsequent migratory capacity of primed, antigen-specific T cells (10)(11)(12) the primed, antigen-specific T cells to visceral organ tumor tissue.…”

LocalSalmonellaimmunostimulation recruits vaccine-specific CD8 T cells and increases regression of bladder tumor

“…1 This can be improved by using appropriate vaccine administration routes, allowing targeting of relevant tumor sites through specific mucosal homing or cancer site retention programs. [2][3][4][5] An alternative approach, irrespective of the immunization route, is to enhance T-cell attraction to the tumor site through the local application of selected chemokines 6 or Toll-like receptor (TLR) agonists that are able to modify the expression of selectins, integrins, chemokines, and chemokine receptors. 7,8 Along this line, we recently reported that intravaginal (IVAG) administration of CpG (a TLR-9 agonist) resulted in the accumulation of CD8 T cells co-expressing CCR5 and CXCR3 chemokine receptors and E-selectin ligands (ESL), most probably through CpG-induced expression of CCL5, CXCL9, CXCL10, CXCL11, and/or E-selectin 9 .…”