{"id":2239,"date":"2025-05-06T11:57:05","date_gmt":"2025-05-06T11:57:05","guid":{"rendered":"https:\/\/blogs.bmj.com\/spcare\/?p=2239"},"modified":"2025-05-15T14:36:47","modified_gmt":"2025-05-15T14:36:47","slug":"sapporo-spring-newsletter","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/spcare\/2025\/05\/06\/sapporo-spring-newsletter\/","title":{"rendered":"Sapporo Spring 2025 Newsletter"},"content":{"rendered":"

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Author:<\/strong> Dr. Kunihiko Ishitani<\/span><\/span><\/em>
\nPresident of The International Research Society of the Sapporo Conference for Palliative and Supportive Care in Cancer\u00a0<\/em>
\nPresident, Higashi Sapporo Hospital, Japan<\/em><\/p>\n

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Introduction<\/span><\/span><\/strong>
\nFor our Spring Newsletter (for full newsletter, see link below) I have been reflecting on immunotherapy and its relation to palliative care. The recent remarkable advances in cancer immunotherapy are now widely recognized not only among healthcare professionals but also by the general public. The field of palliative care for cancer has also entered an era in which its relationship with cancer immunotherapy is being actively explored. In the past, I was involved in research on tumor immunity [1], and I have continued to study tumor immunity through the Department of Pathology at my alma mater, Sapporo Medical University [2]. In this article, I will provide an overview of recent developments in cancer palliative care and tumor immunity based on my experiences.The Philosophy of Palliative Care and Tumor Immunity<\/span><\/span><\/strong>
\nPalliative care is a practice that addresses the human experiences of birth, aging, illness, and death (the four sufferings in Buddhist philosophy) and seeks to safeguard \u2018human dignity\u2019. I believe that the philosophy of palliative care aligns closely with that of the immune system.
\nThe immune system functions as a biological defense mechanism that eliminates non-self-elements. However, cancer cells exploit immunosuppressive mechanisms to proliferate, evade immune surveillance, and assimilate and proliferate into the body as if they were part of the self. Even when cancer immunotherapy proves effective, the immune system accompanies the process throughout the entire journey (the process of birth, aging, illness, and death) and, in doing so, safeguards \u2018human dignity\u2019.Remarkable Advancements in Cancer Immunotherapy<\/span><\/span><\/strong>
\nHistorically, although targeting many diseases, hospice and palliative care developed with a focus on cancer. This is largely because cancer, with its association with \u201cpain,\u201d has been one of the most symbolic, psychologically and physically burdensome illnesses for humans. As previously mentioned, palliative care for cancer has recently entered a new era that places greater emphasis on biology [3].
\nWithin the field of oncology, which underpins this shift, the progress of tumor immunology has been particularly remarkable. Cancer immunotherapy has led to the emergence of long-term survivors (some even appearing to be completely cured) despite being diagnosed with stage IV cancer. The 2016 paper by Samuel J. Harris, titled “Raising the Tail of the Kaplan-Meier Survival Curve” [4], is widely known in this context. The turning point was the introduction of the first immune checkpoint inhibitor, nivolumab, in 2014.
\nThis was followed by the approval of the CAR-T (Chimeric Antigen Receptor T-cell) therapy drug tisagenlecleucel in 2017 and, most recently, the launch of the TCR-T (T-cell Receptor T-cell) therapy drug afamitresgene autoleucel in 2024. These breakthroughs have made cancer immunotherapy one of the most remarkable developments in recent years.
\nHowever, the effectiveness of immune checkpoint inhibitors (ICIs) remains limited. Moreover, immune-related adverse effects (irAEs) pose significant concerns, particularly those involving serious autoimmune reactions. The research on and clinical applications of CAR-T and TCR-T cell therapies, thus, remain in their early stages.The Current State of Tumor Immunology<\/span><\/span><\/strong>
\nTumor immunology has undergone rapid development, evolving from foundational studies on immune responses to clinical applications. One widely recognized conceptual framework is the cancer-immunity cycle [5], an illustrative model that explains anti-tumor immune responses by tumor-specific T cells in seven steps: 1) Release of cancer cell antigens, 2) Cancer antigen presentation (uptake of tumor antigens by antigen-presenting cells and their migration to lymph nodes), 3) Priming and activation (antigen presentation to T cells and activation of antigen-specific T cells), 4) Trafficking of T cells to tumors, 5) Infiltration of T cells into tumors, 6) Recognition of cancer cells by T cells, and 7) Killing of cancer cells.
\nThese seven steps are shown in the figure. As the cycle progresses, tumor cells attacked and killed by T cells release new tumor antigens, leading to a resumption of the process from step 1.
\nIf any step in this cycle is disrupted, effective induction of an anti-tumor immune response becomes difficult, allowing the cancer to escape immune surveillance. For instance, PD-1 (programmed cell death 1) expressed on activated T cells binds to PD-L1 (programmed death-ligand 1) expressed on tumor cells, transmitting an inhibitory signal to the T cell (inhibition at step 7).
\nICIs work by blocking this suppression, restoring the stalled cancer-immunity cycle and reactivating the immune response against the tumor. Research has identified therapeutic strategies targeting each of these steps, with tangible results so far reported.
\nCurrently, clinical research is entering a critical phase, employing cutting-edge technologies such as multi-omics analyses, single-cell immune profiling, genome editing techniques, immunometabolic analysis, and gut microbiota analysis. These approaches are being used in reverse translational research to identify predictive biomarkers for treatment response, guide therapy selection, develop combinatory immunotherapies, and pioneer new methods of cancer control.<\/p>\n
Cancer Immunotherapy in Palliative Care for Cancer<\/span><\/span><\/strong><\/div>\n

In recent years, papers discussing cancer immunotherapy within the field of palliative care have begun to appear with increasing frequency [6\u201310]. Many of these studies are exploratory and focus on the use of ICIs in end-of-life care.
\nA recent US cohort study examined 242,371 patients with stage IV malignancies, including melanoma, non-small cell lung cancer, and renal cell carcinoma. The study found that physicians are increasingly administering ICIs to patients with metastatic cancer at the end of life, and that the initiation of these treatments tends to occur more frequently as the disease progresses. Notably, this trend was more prevalent in non-academic or very low-volume centers than in academic or high-volume centers [11].
\nAlthough such patterns had been observed anecdotally before, this large-scale cohort study provides scientific insights that could inform the future of immunotherapy for patients with advanced cancer [12].
\nWhile the clinical application of ICIs in palliative care holds potential, it should be approached with caution. Looking forward, even within palliative care, research into the mechanisms of immune-related adverse events (irAEs) may open the door to drug development and new therapeutic strategies. Furthermore, areas such as psycho-oncology [13], cost-effectiveness, and broader clinical ethics in the context of immunotherapy are still in their infancy.
\nIt is essential that healthcare providers gain a deeper understanding of tumor immunology to appropriately provide cancer immunotherapy within the framework of palliative care.
\nGiven these developments, it seems that palliative cancer care is now undergoing a significant paradigm shift.<\/p>\n

Conclusion<\/span><\/span><\/strong>
\nPalliative care focuses not on the cancer itself, but on the host; i.e., the patient with cancer. Similarly, cancer immunotherapy targets not the tumor directly, but the patient\u2019s immune system. This parallel structure is truly intriguing and, moreover, it reflects the core of an old yet ever-evolving concept of tumor-host interactions [14,15,16].
\nFurthermore, this framework offers valuable insights when considering the integration of genomic research into tumor immunology, ultimately advancing cancer care as a form of personalized medicine.<\/p>\n<\/div>\n

To read the full newsletter, click here<\/a>.<\/p>\n

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References<\/strong>
\n1, Urushizaki I, Ishitani K et all : Immunosuppressive factors in serum of patients with gastric carcinoma.
\nGANN. 1977. 68(4), 413-421<\/a>
\n2, Miyamoto S, Kanaseki T, Ishitani K, Torigoe T et al : The antigen ASB4 on cancer stem cells serves as a target for CTL immunotherapy of colorectal cancer.
\nCancer. Immunol Res. 2018 .Mar;6(3)358-369
\ndoi: 10.1158\/2326-6066.CIR-17-0518.<\/a>
\n3,\u00a0https:\/\/blogs.bmj.com\/spcare\/2024\/11\/15\/autumn-newsletter-of-the-international-research-society-sapporo-japan\/<\/a>
\n4,\u00a0Harris SJ, et al : Immuno-oncology combinations: raising the tail of the survival curve. Cancer Bio Med. 2016. Jun; 13(2):171-193.
\ndoi:10.20892\/j-issn.2095-3941.2016.0015.<\/a>
\n5, Chen DS, Meliman I : Oncology meets immunology: The cancer-immunity cycle.Immunity.2013.39,July25:1-10\u00a0http:\/\/dx.doi.org\/10.1016\/j.immuni.2013.07.012<\/a>
\n6, Davis MP, Panikkar R : Checkpoit inhibitors, palliative care, or hospice. Curr Oncol Rep. 2018. 20:2.\u00a0https:\/\/doi.org\/10.1007\/s11912-018-0659-0<\/a>
\n7, Glisch C, et al : Immune checkpoint inhibitor use near the end of life is associated with poor performance status, lower hospice enrollment, and dying in the hospital. Am J Hosp Palliat Care .2020.37:179-184
\nhttps\/\/doi.org\/10.1177\/1049909119862785<\/a>
\n8, Petrillo LA, et al : Performance status and end-of-life care among adults with non-small cell lung cancer receiving immne checkpont inhibitors. Cancer. 2020
\n126:2288-2295. https:\/\/doi.org\/10.1002\/cncr.32782
\n9, Auclair J, et al : Duration of palliative care involvement and immunotherapy treatment near the end of life among patients with cancer who died in-hospital.
\nSupport Care Cancer. 2022. Jun;30(6):4997-5006.
\ndoi : 10.1007\/s00520-022-06901-1<\/a>
\n10, Zanichelli A : The role of immunotherapy in palliative care for cancer patients.
\nImmunome Res. 2023.Mar;19(222).\u00a0doi: 10.35248\/1745-7580.23.19.222<\/a>
\n11, Kerekes DM, et al : Imunotherapy initiation at the end of life in patients with metastatic cancer in the US. JAMA Oncol.2024;10(3):342-351.
\ndoi: 10.1001\/jamaoncol.2023.6025<\/a>
\n12, Harris E : Gaps exist in end-of-life immunotherapy treatment for cancer. JAMA.2024;331(6):467.\u00a0doi:10.1001\/jama.2023.27972<\/a>
\n13, Sun W, et al : Symptoms of hematologic tumors patients after CAR-T therapy:
\nA systematic review and meta-analysis. J Pain Symptom Manage. 2025 Mar;69(3):304-317.doi: 10.1016\/j.jpainsymman.2024.11.002.<\/a>
\n14, Sassenrath EN, et al: Tumor-host relationships:\u00a0\u2162. Composition studies on experimental tumors.\u00a0Cancer Res. 1958 May;18(4):433-439<\/a>
\n15, Hiam-Galvez KJ, et al : Systemic immunity in cancer. Nat Rev Cancer.2021 Jun;21(6):345-359.doi:10.1038\/s41568-021-00347-z<\/a>
\n16, Celebrating a decade of the Journal for Immuno Therapy of Cancer JITC. 2022. May; 10(5)eoo5207.doi; 10.1136\/jitc-2022-005207<\/a><\/p>\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

Author: Dr. Kunihiko Ishitani President of The International Research Society of the Sapporo Conference for Palliative and Supportive Care in Cancer\u00a0 President, Higashi Sapporo Hospital, Japan Introduction For our Spring Newsletter (for full newsletter, see link below) I have been reflecting on immunotherapy and its relation to palliative care. The recent remarkable advances in cancer […]<\/p>\n

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