In epithelium-enriched areas, immune signals were also detectable and varied by subtype, with regulatory T-cell markers being higher in Basal-like vs. Luminal breast cancer.
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Walens, A., Olsson, L. T., Gao, X., Hamilton, A. M., Kirk, E. L., Cohen, S. M., Midkiff, B. R., Xia, Y., Sherman, M. E., Nikolaishvili-Feinberg, N., Serody, J. S., Hoadley, K. A., Troester, M. A., & Calhoun, B. C. (2021). Protein-based immune profiles of basal-like vs. luminal breast cancers. Laboratory Investigation, 1–9. https://doi.org/10.1038/s41374-020-00506-0 Cite
Scientists describe the results from a Phase Ib clinical trial in which 17 patients with locally advanced head and neck squamous cell carcinoma received a murine anti-human OX40 agonist antibody prior to definitive surgical resection.
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Duhen, R., Ballesteros-Merino, C., Frye, A. K., Tran, E., Rajamanickam, V., Chang, S.-C., Koguchi, Y., Bifulco, C. B., Bernard, B., Leidner, R. S., Curti, B. D., Fox, B. A., Urba, W. J., Bell, R. B., & Weinberg, A. D. (2021). Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. Nature Communications, 12(1), 1047. https://doi.org/10.1038/s41467-021-21383-1 Cite
Scientists discovered that brain tumor cells had a particularly high demand for oxygen, which affected γδ T cell-mediated antitumor immune responses but not those of conventional T cells.
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Park, J. H., Kim, H.-J., Kim, C. W., Kim, H. C., Jung, Y., Lee, H.-S., Lee, Y., Ju, Y. S., Oh, J. E., Park, S.-H., Lee, J. H., Lee, S. K., & Lee, H. K. (2021). Tumor hypoxia represses γδ T cell-mediated antitumor immunity against brain tumors. Nature Immunology, 1–11. https://doi.org/10.1038/s41590-020-00860-7 Cite
Researchers explored the ability of a humanized radiolabeled CD8-targeted minibody to non-invasively quantify tumor-infiltrating CD8+ T cells using positron emission tomography.
[Clinical Cancer Research]
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Nagle, V. L., Henry, K. E., Hertz, C. A. J., Graham, M. S., Campos, C., Parada, L. F., Pandit-Taskar, N., Schietinger, A., Mellinghoff, I. K., & Lewis, J. S. (2021). Imaging Tumor-Infiltrating Lymphocytes in Brain Tumors with [64Cu]Cu-NOTA-anti-CD8-Positron Emission Tomography. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-20-3243 Cite
Scientists recruited 33 lung cancer patients with brain oligo-metastasis to explore the genomic features and tumor immune microenvironment of the lung and brain metastasis independently.
[Cell Death & Disease]
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Song, Z., Yang, L., Zhou, Z., Li, P., Wang, W., Cheng, G., Chen, R., Chang, L., Zhang, Y., Guan, Y., Xia, X., Yi, X., Zhou, R., & Chen, M. (2021). Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis. Cell Death & Disease, 12(1), 1–10. https://doi.org/10.1038/s41419-021-03410-7 Cite
Tumor-reactive tumor-infiltrating lymphocytes were detected in half of patients and were exclusively present in cells derived from the PD-1+ fraction.
[British Journal of Cancer]
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Salas-Benito, D., Conde, E., Tamayo-Uria, I., Mancheño, U., Elizalde, E., Garcia-Ros, D., Aramendia, J. M., Muruzabal, J. C., Alcaide, J., Guillen-Grima, F., Minguez, J. A., Amores-Tirado, J., Gonzalez-Martin, A., Sarobe, P., Lasarte, J. J., Ponz-Sarvise, M., De Andrea, C. E., & Hervas-Stubbs, S. (2021). The mutational load and a T-cell inflamed tumour phenotype identify ovarian cancer patients rendering tumour-reactive T cells from PD-1 + tumour-infiltrating lymphocytes. British Journal of Cancer, 1–12. https://doi.org/10.1038/s41416-020-01218-4 Cite
Investigators report an inverse correlation between glutamine metabolic genes and markers of T cell-mediated cytotoxicity in human basal-like breast cancer patient datasets, with increased glutamine metabolism and decreased T cell cytotoxicity associated with poor survival.
[Journal of Clinical Investigation]
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Edwards, D. N., Ngwa, V. M., Raybuck, A. L., Wang, S., Hwang, Y., Kim, L. C., Cho, S. H., Paik, Y., Wang, Q., Zhang, S., Manning, H. C., Rathmell, J. C., Cook, R. S., Boothby, M. R., & Chen, J. (2020). Selective glutamine metabolism inhibition in tumor cells improves anti-tumor T lymphocyte activity in triple-negative breast cancer. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI140100 Cite
The authors report that loss of RANK signaling in mouse tumor cells increased leukocytes, lymphocytes, and CD8+ T cells, and reduced macrophage and neutrophil infiltration.
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Gómez-Aleza, C., Nguyen, B., Yoldi, G., Ciscar, M., Barranco, A., Hernández-Jiménez, E., Maetens, M., Salgado, R., Zafeiroglou, M., Pellegrini, P., Venet, D., Garaud, S., Trinidad, E. M., Benítez, S., Vuylsteke, P., Polastro, L., Wildiers, H., Simon, P., Lindeman, G., … González-Suárez, E. (2020). Inhibition of RANK signaling in breast cancer induces an anti-tumor immune response orchestrated by CD8+ T cells. Nature Communications, 11(1), 6335. https://doi.org/10.1038/s41467-020-20138-8 Cite
Using high-dimensional analysis of human adoptive T cell therapy products, scientists identified a memory-progenitor CD39-negative stem-like phenotype associated with complete cancer regression and tumor-infiltrating lymphocyte (TIL) persistence and a terminally differentiated CD39-positive state associated with poor TIL persistence.
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Krishna, S., Lowery, F. J., Copeland, A. R., Bahadiroglu, E., Mukherjee, R., Jia, L., Anibal, J. T., Sachs, A., Adebola, S. O., Gurusamy, D., Yu, Z., Hill, V., Gartner, J. J., Li, Y. F., Parkhurst, M., Paria, B., Kvistborg, P., Kelly, M. C., Goff, S. L., … Rosenberg, S. A. (2020). Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer. Science, 370(6522), 1328–1334. https://doi.org/10.1126/science.abb9847 Cite
Scientists studied the effects of high-dose per fraction radiotherapy with and without anti-Gr-1 using syngeneic murine allograft prostate cancer models. The dynamic change of immune populations, including tumor-infiltrating lymphocytes, T-regulatory cells, and myeloid-derived suppressive cells was evaluated using flow cytometry and immunohistochemistry.
[Clinical Cancer Research]
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High-Dose per Fraction Radiotherapy Induces Both Anti-Tumor Immunity and Immunosuppressive Responses in Prostate Tumors | Clinical Cancer Research. (n.d.). Retrieved November 24, 2020, from https://clincancerres.aacrjournals.org/content/early/2020/11/20/1078-0432.CCR-20-2293 Cite
Scientists investigated the potential correlation between clinical outcomes and peripheral blood immune cell profiles, specifically focused on FoxP3+ Treg cells, collected at baseline and one week after anti-PD-1 therapy in two independent cohorts of patients with NSCLC.
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Koh, J., Hur, J. Y., Lee, K. Y., Kim, M. S., Heo, J. Y., Ku, B. M., Sun, J.-M., Lee, S.-H., Ahn, J. S., Park, K., & Ahn, M.-J. (2020). Regulatory (FoxP3 + ) T cells and TGF-β predict the response to anti-PD-1 immunotherapy in patients with non-small cell lung cancer. Scientific Reports, 10(1), 18994. https://doi.org/10.1038/s41598-020-76130-1 Cite