Clinical and immune profiling for cancer of unknown primary site

J Immunother Cancer. 2019 Sep 13;7(1):251. doi: 10.1186/s40425-019-0720-z.

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.

Keywords: Cancer of unknown primary site (CUP); Gene expression; Immune checkpoint inhibitor; Immune profile; Immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / analysis
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology*
  • B7-H1 Antigen / metabolism
  • Datasets as Topic
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Monitoring, Immunologic / methods
  • Neoplasms, Unknown Primary / drug therapy
  • Neoplasms, Unknown Primary / immunology*
  • Neoplasms, Unknown Primary / mortality
  • Neoplasms, Unknown Primary / pathology
  • Patient Selection
  • Retrospective Studies

Substances

  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human