Clinical and immune profiling for cancer of unknown primary site

Koji Haratani, Hidetoshi Hayashi, Takayuki Takahama, Yasushi Nakamura, Shuta Tomida, Takeshi Yoshida, Yasutaka Chiba, Takahiro Sawada, Kazuko Sakai, Yoshihiko Fujita, Yosuke Togashi, Junko Tanizaki, Hisato Kawakami, Akihiko Ito, Kazuto Nishio, Kazuhiko Nakagawa

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) confer a survival benefit in many cancer types. Given that the survival outcome for cancer of unknown primary site (CUP) remains poor, we investigated the potential of CUP for immunotherapy. METHODS: A total of 164 patients with CUP (favorable subset, 34 patients; unfavorable subset, 130 patients) who were treated between January 2009 and March 2017 was identified from a review of medical records at Kindai University Hospital. They included 92 patients for whom pretreatment tumor tissue was available both for determination of programmed cell death-ligand 1 expression and tumor-infiltrating lymphocyte (TIL) density by immunohistochemistry (IHC) and for immune-related gene expression profiling (irGEP). The results of irGEP for CUP were compared with published data for ICI-treated solid cancers classified into progressive disease (PD) and non-PD subsets according to their best response to ICIs. RESULTS: The median overall survival of all CUP patients was 29.3 months (95% confidence interval [CI], 15.7-not reached) and 7.1 months (95% CI, 5.0-9.4) for favorable and unfavorable subsets, respectively. IHC and irGEP revealed that pretreatment immune activity-including expression of immune checkpoint molecules-for CUP was similar to that for ICI-responsive malignancies (antitumor immune cell signatures: CUP versus PD, P = 0.002-0.067; CUP versus non-PD, P = 0.591-0.999), although VEGFA expression was associated with suppression of antitumor immunity in CUP (P = 0.008, false discovery rate = 0.010). In addition, one case of CUP in the unfavorable subset that was associated with prominent PD-L1 expression on TILs and showed a durable response to nivolumab is presented. CONCLUSIONS: The survival outcome of CUP remains unsatisfactory. However, our clinical and immune profiling of CUP has revealed a potential to benefit from immunotherapy, with ICIs thus being a potential option for CUP treatment.

Original languageEnglish
Number of pages1
JournalJournal for immunotherapy of cancer
Volume7
Issue number1
DOIs
Publication statusPublished - Sep 13 2019

Keywords

  • Cancer of unknown primary site (CUP)
  • Gene expression
  • Immune checkpoint inhibitor
  • Immune profile
  • Immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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  • Cite this

    Haratani, K., Hayashi, H., Takahama, T., Nakamura, Y., Tomida, S., Yoshida, T., Chiba, Y., Sawada, T., Sakai, K., Fujita, Y., Togashi, Y., Tanizaki, J., Kawakami, H., Ito, A., Nishio, K., & Nakagawa, K. (2019). Clinical and immune profiling for cancer of unknown primary site. Journal for immunotherapy of cancer, 7(1). https://doi.org/10.1186/s40425-019-0720-z