Vaccination against galectin-1 promotes cytotoxic T-cell infiltration in melanoma and reduces tumor burden

2022 ◽  
Author(s):  
Julia Femel ◽  
Luuk van Hooren ◽  
Melanie Herre ◽  
Jessica Cedervall ◽  
Falk Saupe ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Burden ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
T Cell Infiltration

scholarly journals Modelling the interplay between the CD4$$^{+}$$/CD8$$^{+}$$ T-cell ratio and the expression of MHC-I in tumours

2021 ◽  
Vol 83 (1) ◽  
Author(s):  
Christian John Hurry ◽  
Alexander Mozeika ◽  
Alessia Annibale
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Critical Level ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
Mhc I ◽  
Cell Ratio ◽  
T Cell Infiltration ◽  
Immunological Mechanisms ◽  
Tcr Repertoire

AbstractDescribing the anti-tumour immune response as a series of cellular kinetic reactions from known immunological mechanisms, we create a mathematical model that shows the CD4$$^{+}$$ + /CD8$$^{+}$$ + T-cell ratio, T-cell infiltration and the expression of MHC-I to be interacting factors in tumour elimination. Methods from dynamical systems theory and non-equilibrium statistical mechanics are used to model the T-cell dependent anti-tumour immune response. Our model predicts a critical level of MHC-I expression which determines whether or not the tumour escapes the immune response. This critical level of MHC-I depends on the helper/cytotoxic T-cell ratio. However, our model also suggests that the immune system is robust against small changes in this ratio. We also find that T-cell infiltration and the specificity of the intra-tumour TCR repertoire will affect the critical MHC-I expression. Our work suggests that the functional form of the time evolution of MHC-I expression may explain the qualitative behaviour of tumour growth seen in patients.

P1602MICROVASCULAR INFLAMMATION WITHOUT DSA OR C4D: AN ORPHAN CATEGORY IN BANFF CLASSIFICATION WITH INTENSE CAPILLARITIS AND CYTOTOXIC T-CELL INFILTRATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anna Buxeda ◽  
Laura Llinàs ◽  
Javier Gimeno ◽  
Carlos Arias Cabrales ◽  
Carla Burballa Tarrega ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
T Cell ◽  
Nk Cells ◽  
Lymphocyte Subsets ◽  
Normal Group ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
Antibody Mediated Rejection ◽  
T Cell Infiltration ◽  
Peritubular Capillaries

Abstract Background and Aims Antibody-mediated rejection (ABMR) associated with donor-specific HLA antibodies (DSA) is the leading cause of late allograft failure after kidney transplantation. Microvascular inflammation (MVI) without detectable circulating DSA or C4d + cannot be classified as ABMR according to Banff-2017. The involvement of intragraft lymphocyte subsets in the development of humoral damage in kidney transplantation (KT) is relevant. We aimed to analyze lymphocyte subset distribution in kidney transplant biopsies (KTBx) with ABMR compared with MVI and with normal KTBx. Method KTBx with ABMR, MVI (g+ptc≥2, without DSA) or normal findings were included. DSA were identified with Luminex single antigen assays. Intragraft lymphocyte subsets’ characterization was performed by immunohistochemistry: T-lymphocytes (CD3, CD4, CD8, Foxp3), B-lymphocytes / plasmatic cells (CD20, CD138), NK cells (CD56), macrophages / monocytes (CD68), cytotoxic cells (TIA1) and activated cells (PD1) were evaluated. Results We analyzed 34 KTBx: 21 ABMR, 5 MVI and 8 KTBx with normal findings. KT with ABMR and MVI had more proteinuria at the time of the biopsy compared with the normal group (575 mg/24h and 964 mg/24h vs 147 mg/24h, p=0.002 and p=0.005 respectively). DSA were more frequently detected in patients with ABMR (95.2% vs 0% and 37.5%, p<0.001 and p=0.003 respectively). KTBx with ABMR and MVI had increased cytotoxic T-cell infiltration apparently corresponding to NK cells in peritubular capillaries (ptc) compared to normal group. Moreover, both groups showed a greater number of macrophages and monocytes in glomeruli. KT with MVI but not with ABMR had a significantly increased activated cell infiltration (PD1+) in ptc compared to the normal group, and showed an increased cytotoxic T-cell infiltration in glomeruli compared to ABMR and normal groups. Conclusion ABMR and MVI have an increased infiltration of NK cells with cytotoxic activity in ptc that differs from the normal group. However, KT with MVI show greater infiltration of activated cells in ptc and cytotoxic T-cell in glomeruli compared to ABMR suggesting the possibility of different activation pathways.

scholarly journals Therapeutic Induction of Tertiary Lymphoid Structures in Cancer Through Stromal Remodeling

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna Johansson-Percival ◽  
Ruth Ganss
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Tumor Rejection ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
T Cell Infiltration ◽  
Anti Cancer ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

Improving the effectiveness of anti-cancer immunotherapy remains a major clinical challenge. Cytotoxic T cell infiltration is crucial for immune-mediated tumor rejection, however, the suppressive tumor microenvironment impedes their recruitment, activation, maturation and function. Nevertheless, solid tumors can harbor specialized lymph node vasculature and immune cell clusters that are organized into tertiary lymphoid structures (TLS). These TLS support naïve T cell infiltration and intratumoral priming. In many human cancers, their presence is a positive prognostic factor, and importantly, predictive for responsiveness to immune checkpoint blockade. Thus, therapeutic induction of TLS is an attractive concept to boost anti-cancer immunotherapy. However, our understanding of how cancer-associated TLS could be initiated is rudimentary. Exciting new reagents which induce TLS in preclinical cancer models provide mechanistic insights into the exquisite stromal orchestration of TLS formation, a process often associated with a more functional or “normalized” tumor vasculature and fueled by LIGHT/LTα/LTβ, TNFα and CC/CXC chemokine signaling. These emerging insights provide innovative opportunities to induce and shape TLS in the tumor microenvironment to improve immunotherapies.

scholarly journals Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration

Cell Reports ◽  
2019 ◽  
Vol 29 (8) ◽  
pp. 2338-2354.e7 ◽  
Author(s):  
Hye-Jung E. Chun ◽  
Pascal D. Johann ◽  
Katy Milne ◽  
Marc Zapatka ◽  
Annette Buellesbach ◽  
...  
Keyword(s):  
T Cell ◽  
Rhabdoid Tumor ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
Molecular Subgroups ◽  
T Cell Infiltration

scholarly journals In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor

2007 ◽  
Vol 176 (4) ◽  
pp. i8-i8
Author(s):  
Alexandre Boissonnas ◽  
Luc Fetler ◽  
Ingrid S. Zeelenberg ◽  
Stéphanie Hugues ◽  
Sebastian Amigorena
Keyword(s):  
T Cell ◽  
Solid Tumor ◽  
In Vivo Imaging ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
T Cell Infiltration

scholarly journals Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhenqing Wang ◽  
Liang Chen ◽  
Yiqun Ma ◽  
Xilei Li ◽  
Annan Hu ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Near Infrared ◽  
Peptide Vaccine ◽  
Immune Checkpoint Blockade ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
Immunogenic Cell Death ◽  
T Cell Infiltration

AbstractThe clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.

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